Journal Pre-proof

Descemet Membrane Detachment

Deepali Singhal, MD, Pranita Sahay, MD, Siddhi Goel, MD, Mohamed Ibrahime Asif,
MD, Prafulla K. Maharana, MD, Namrata Sharma, MD

PII: S0039-6257(20)30002-3
DOI: https://doi.org/10.1016/j.survophthal.2019.12.006
Reference: SOP 6920

To appear in: Survey of Ophthalmology

Received Date: 12 July 2019

Revised Date: 27 December 2019
Accepted Date: 30 December 2019

Please cite this article as: Singhal D, Sahay P, Goel S, Asif MI, Maharana PK, Sharma N,
Descemet Membrane Detachment, Survey of Ophthalmology (2020), doi: https://doi.org/10.1016/
j.survophthal.2019.12.006.

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1 Descemet Membrane Detachment

3 Deepali Singhal1, MD

4 Pranita Sahay2, MD

5 Siddhi Goel2, MD

6 Mohamed Ibrahime Asif 2, MD

7 Prafulla K. Maharana2, MD

8 Namrata Sharma2, MD

10 Affiliation: 1Eye-Q Vision Pvt. Ltd., Max Multi-specialty Centre, Noida and

11 Vaishali, Uttar Pradesh, India.

2
12 Department of Ophthalmology, Dr. Rajendra Prasad Centre for Ophthalmic

13 Sciences, All India Institute of Medical Sciences, New Delhi, India.

14 Corresponding author

15 Namrata Sharma, MD

16 Professor of Ophthalmology

17 Cornea, Cataract and Refractive Surgery services

18 Dr. Rajendra Prasad Centre for Ophthalmic Sciences

19 All India Institute of Medical Sciences, New Delhi, India

20 Email: [email protected]

21 Fax No: 91-11-26588919, Tel- 91-9810856988

22 Declarations of interest: None

1
23 Abstract

24 Descemet membrane detachment (DMD) is a potential vision-threatening

25 complication that occurs most commonly after cataract surgery. DMD has also

26 been reported to occur in various other surgeries like keratoplasty, iridectomy,

27 vitrectomy, trabeculectomy, holmium laser sclerostomy, alkali burn, and

28 viscocanalostomy. Major risk factors include advanced age, preexisting

29 endothelial diseases like Fuchs dystrophy or abnormality in the Descemet

30 membrane and stromal interface, hard cataract, prolonged surgical time,

31 ragged clear corneal incisions, and inadvertent trauma with blunt instruments

32 or phacoemulsification probe. Most DMDs are peripheral and resolve

33 spontaneously. Large, central DMD’s if not managed appropriately, may lead

34 to corneal decompensation and opacification. Several authors have classified

35 DMD depending upon its configuration, height, extent, length and position with

36 respect to pupil. Anterior segment optical coherence tomography has been

37 used to confirm and classify DMD and can also aid in deciding the

38 management plan. Spontaneous reattachment of the DM with conservative

39 management may occur in cases with small, peripheral, planar DMD with non-

40 scrolled edges. Cases with non-planar, central DMD, scrolled edges, and

41 length >2mm, however, have to be managed surgically. Descemetopexy is

42 the gold standard for the management of DMD. Other management options

43 include mechanical tamponade, suture fixation, descemetotomy, interface

44 drainage and keratoplasty. Prompt diagnosis and timely management often

45 leads to a good visual outcome.

2
46 Keywords: Descemet membrane detachment; Anterior segment optical

47 coherence tomography; Descemet membrane; Perfluoropropane;

48 descemetopexy.

49 1. Introduction

50 Descemet membrane (DM), the basement membrane of the corneal

51 endothelium, (8–10 µm thick) contributes in maintaining the corneal

52 transparency along with the endothelium. Weve and coworkers identified and

53 named Descemet membrane detachment (DMD) in 1927, while Samuels first

54 classified it in 1928.4,64 DMD has been characterized as a potential vision-

55 threatening complication and has been reported to occur in almost 43% of

56 cases after cataract surgery.71 Cataract is one of the major causes of

57 blindness and contributes to 51% of world blindness (2010).80 In developing

58 countries like India, more than 50% blindness is from cataracts (62.6%).15

59 Phacoemulsification and manual small incision cataract surgery are the most

60 effective and commonly performed procedures. DMD can also occur in

61 various other surgeries such as iridectomy, corneal transplantation,

62 vitrectomy, trabeculectomy, holmium laser sclerostomy, hydrogen peroxide

63 injury, alkali burn, and viscocanalostomy.71 Most DMDs resolve

64 spontaneously within days after surgery.

65 We update the pathogenesis, clinical features, investigations, diagnoses, and

66 management modalities of DMD.

67 2. Clinical anatomy

68 2.1. Descemet membrane

69 DM consists of a thin (0.3 µm), non-banded layer adjacent to the stroma, an

70 anterior banded zone (2–4 µm), and a posterior, non-banded zone (>4 µm).

3
71 The posterior non-banded zone represents up to two-thirds of the thickness of

72 the DM.36 The anterior banded layer has been reported to develop at five

73 months of gestation in the fetus and having a thickness of approximately 3 µm

74 following which its thickness and structure remains constant throughout life,

75 whereas the posterior non- banded layer develops only after birth, and its

76 thickness increases significantly with age--around 1 µm every decade

77 (approximately 2 µm at the age of 10 to 10 µm at the age of 80).38

78 It is primarily composed of collagen types IV and VIII, along with the non-

79 collagenous components such as fibronectin, laminin, nidogen, vitronectin,

80 perlecan, as well as keratan, heparin, dermatan, and chondroitin sulfate

81 proteoglycans.21,23,75 Type VIII collagen, produced by the corneal

82 endothelium, has a structure quite different from type IV collagen since it

83 forms a hexagonal lattice in the basement membrane. DM plays an important

84 role in several physiologic processes such as corneal hydration, endothelial

85 cell differentiation and proliferation, and maintenance of the corneal curvature,

86 apart from providing structural integrity of the cornea.65

87 The DM does not have the capacity to regenerate after any damage or

88 rupture in cases of hydrops. Primary abnormality in the DM has been reported

89 in Fuchs endothelial dystrophy which is associated with a mutation in COL8A2

90 gene, encoding for α2 chain of type VIII collagen and resulting in deposition of

91 an atypical striated pattern of posterior collagen layer in the DM.7,8 An atomic

92 force microscopy nanoindentation analysis of the human DM has shown that it

93 has a highly discontinuous, corrugated and a porous nature and is made of a

94 tangle of collagen/proteoglycans structures.14

95 2.2. DM stromal interaction

4
96 DM is tightly attached to the posterior corneal stroma by a narrow transitional

97 zone of amorphous extracellular matrix known as the interfacial matrix.65

98 Thus, the rupture of the DM leads to penetration of aqueous humor into the

99 corneal stroma and subsequent stromal edema. It has been reported that

100 there is a physiologic cleavage plane that exists between the interfacial

101 matrix, the anterior most adhesive zone of DM, and the corneal stroma, that

102 can be disrupted by mechanical forces, thus suggesting a weak attachment.65

103 The ultra-structural analysis of the Descemet membrane and stromal interface

104 (DSI) has revealed the presence of three components. First is the amorphous

105 interfacial matrix, second component is the thin meshwork of randomly

106 arranged collagen fibrils projecting from the posterior stroma into the anterior

107 DM zone and the third component is made of proteoglycan filaments. The

108 interfacial matrix represents the adhesive zone of DM and is composed of

109 various extra- cellular matrix proteins with adhesive properties, such as

110 fibronectin, amyloid P, osteonectin, fibrillin-1, fibulin-1, fibulin-2, fibulin-3, and

111 keratoepithelin as detected by light and electron microscopic

112 immunohistochemistry.65 Among these, keratoepithelin protein (transforming

113 growth factor- b-induced/ TGF-b-induced) and collagen type VI serve as the

114 main anchoring proteins.66 Schlötzer-Schrehardt and coworkers reported that

115 the differences between distances of stromal keratocytes increase

116 significantly from central to the mid- peripheral and peripheral cornea,

117 whereas there is no significant difference between the mean numbers of

118 collagen lamellae in the DSI. This interface consists of 0.5 to 1 µm thick

119 randomly arranged, irregular interwoven lattice of collagen fibers similar to the

5
120 Bowman layer and positive for collagen type III and VI on

121 immunofluorescence.66

122 Cabrerizo and coworkrs determined the microscopic characteristics of the DSI

123 during Descemet membrane endothelial keratoplasty (DMEK) graft

124 preparation using scanning electron microscopy (SEM).9 DSI appears as a

125 straight, black line when viewed with SEM and has been divided into three

126 regions (central: 0–2 mm from the center of the cornea, mid-peripheral: 2–4

127 mm from the center of the cornea and peripheral: 4–5.5 mm form the center of

128 the cornea). The central part does not have any adhesions and has been

129 described as a smooth black line. Minor long thread-like adhesions have been

130 reported in the mid-peripheral area whereas major bridge-like adhesions have

131 been noted in the periphery of the interface, which, are known to become

132 larger and broader in the extreme periphery (5–5.5 mm).9 DSI has been

133 described previously using transmission electron microscopy and

134 immunohistochemistry as amorphous material of the interfacial matrix and

135 posterior stromal fibers projecting into the extracellular matrix of the DM.65

136 3. Etiopathogenesis

137 The most common cause of DMD is after intraocular surgery; however, it is

138 also known to occur spontaneously or as the result of familial, bilateral and

139 late onset post-surgical causes. These might explain the role of some intrinsic

140 DM abnormalities or endothelial diseases. The mechanisms proposed for

141 such causes of DMD include abnormality in the DSI or the fibrillary stromal

142 attachment to the DM, and mutation of the TGF-b induced gene leading to

143 dysfunction of the keratoepithelin protein and thereby resulting in weak

144 adhesions of the DM to the posterior corneal stroma.28,40 This loose

6
145 attachment between the DM and the posterior stromal layer can be easily

146 separated with minimal external force.

147 4. Risk factors

148 There are various risk factors for DMD that can be classified into pre-

149 operative patient related, intraoperative and post- operative factors (Table 1).

150 4.1. Patient-related factors

151 Various pre-operative patients related factors might predispose to DMD such

152 as age over 65 years, preexisting endothelial diseases like Fuchs dystrophy,

153 and intrinsic DSI abnormalities. Presence of mature or dense cataract,

154 uncooperative patient, lack of sufficient anesthesia or a previous history of

155 ocular trauma like alkaline injuries, bleeding from corneal vascularization, or

156 rarely, in atypical keratoconic eyes might also contribute to DMD.4,12,27

157 4.2. Intraoperative factors

158 Intra-operative factors increasing the risk of DMD after cataract surgery

159 include clear corneal incisions that might create lateral traction, thereby

160 causing the separation of loosely attached DM, use of blunt blades for

161 creating incisions, inadvertent insertion of instruments between the stroma

162 and DM, entry into the anterior chamber in a soft globe, tight or small incisions

163 as compared to the size of the phacoemulsification probe and improper

164 incisions like shelved or oblique incisions. Titiyal and coworkers report that

165 ragged slit morphology of the proximal opening of clear corneal incisions

166 (CCI) is the most important predictive factor for incision-site DMD.77 Also,

167 femtosecond-laser CCIs have less incision-site DMD as compared to

168 keratome-assisted CCIs.77

7
169 In addition, direct engagement of the DM after a small detachment into the

170 phacoemulsification or irrigation/aspiration probe or during intraocular lens

171 insertion and shallow anterior chamber also predispose to DMD. Inadvertent

172 injection of substances like saline, air, antibiotics, or viscoelastic between the

173 posterior stroma, especially by novice surgeons, also contributes to the

174 occurrence of DMD.4,27 Sharma and coworkers determined that total

175 ultrasound time over 60 seconds is a significant risk factor of incision site

176 DMD in phacoemulsification along with a higher cumulative dissipated

177 energy.69

178 4.3. Postoperative factors

179 Delayed presentation of DMD, weeks or more after an uncomplicated surgery,

180 has been reported, along with bilateral DMD.20,40 This presentation has led us

181 to believe in various familial and genetic causes of weak adhesion between

182 DM and posterior corneal stroma, irrespective of the type of incision or

183 method of cataract extraction surgery.12

184 Fang and coworkers investigated the role of pre-existing endothelial

185 abnormalities in bilateral postoperative DMDs using specular microscopy and

186 recommended pre-operative counseling and careful endothelial evaluation of

187 the contralateral eye in patients with prior history of DMD. They also

188 recommended that a superior incision would be more beneficial to facilitate

189 management of post- operative gas tamponade in the event of a DMD as

190 compared to a temporal incision.20

191 5. Natural course

192 DMD is not a rare complication after intraocular surgery. The natural history of

193 DMD has been controversial, and the exact timing of intervention still remains

8
194 unclear. Most DMDs remain small and localized to the wound area with no

195 visual complaints, whereas some present with marked diminution of vision

196 from severe corneal edema if the detachment is extensive. DMD has been

197 reported to occur after cataract surgery in almost 43% of cases. Most of them

198 are not significant and resolve spontaneously within days after surgery.

199 If a DMD is extensive, its spontaneous resolution is unlikely because of the

200 collection of fluid in the supra-DM compartment as the DM-endothelial

201 complex receives nutrition from the aqueous. The natural history of DMD

202 is uncertain and unpredictable. Even extensive DMD's also can have a

203 spontaneous resolution. The instances where spontaneous resolution

204 most likely fails is where there has been an extensive trauma to the

205 endothelial cells as a result of which the endothelial pump function is

206 compromised; secondly when there are fibrous/ traction bands

207 which prevents spontaneous attachment. Fibrosis and scarring at DM

208 can both be the cause and effect of long-standing detachment.

209 Because of the compromised endothelial pump function, extensive DMDs, if

210 not addressed at the appropriate time, may lead to corneal decompensation

211 and opacification, resulting in significant visual loss or non-improvement in

212 vision after intraocular surgery.

213 6. Clinical features

214 DMD has been described to occur following various ocular surgeries like

215 cataract surgery being the most common cause, keratoplasty, glaucoma

216 surgeries, and radial keratotomy.

217 6.1. Following cataract surgery

9
218 Among all intraocular surgeries, DMD is most commonly described after

219 cataract surgery. Monroe and coworkers reported a high incidence (43%) of

220 focal DMD that were mostly subclinical and detected only with gonioscopy.57

221 The incidence of visually significant DMD after extracapsular surgery and

222 phacoemulsification is reported to be 2.6% and 0.5% respectively;59 however,

223 the most recent reports establish an incidence of 0.044% to 0.52% after

224 phacoemulsification surgery.41,76

225 6.1.1. Symptoms

226 Patients with DMD after cataract surgery present with poor visual

227 improvement or diminution of vision in cases with delayed presentation. This

228 is associated with localized or diffuse corneal edema, depending upon the

229 location and extent of DMD (Figure 1a, 1b).

230 6.1.2. Signs

231 DMD is usually seen as a translucent membrane in the anterior chamber, at

232 the site of corneal incision or DM perforation. It presents early as localized or

233 diffuse corneal edema over the area of DMD and later progresses to

234 persistent corneal edema (>2 weeks) (Figure 1a, 1b). A double anterior

235 chamber might also be seen in cases with central and extensive DMDs.

236 Gradually with time, the corneal edema increases leading to obscuration of

237 the details of the detached DM. Any case with severe postoperative corneal

238 edema should be investigated to rule out DMD so that timely intervention can

239 be performed.

240 6.2. Following keratoplasty

241 Spontaneous DMD has been reported after both penetrating keratoplasty (PK)

242 as well as anterior lamellar keratoplasty (DALK).26,29,46 The onset of DMD

10
243 varies from 1 month to 30 years post-operatively after PK. This has been

244 reported in only 5 cases where the most common indication for PK was

245 corneal ectasia (keratoconus: 3/5, pellucid marginal degeneration: 1/5), with

246 one case of regraft.

247 Gorski and coworkers reported 2 cases of spontaneous DMD 20 years after

248 PK for keratoconus that had peripheral corneal thinning and steepening

249 without any sign of rejection.26 DM detachment was localized to the area of

250 the corneal edema. Both the cases required Descemet stripping automated

251 endothelial keratoplasty (DSAEK) later. They proposed two mechanisms for

252 DMD including the presence of a retrocorneal membrane (though not proven

253 histopathologically) along the graft-host interface that can cause mechanical

254 detachment of DM and progressive keratoconus in the peripheral host tissue

255 leading to DMD. Both the cases had progressive thinning and steepening in

256 the host and graft-host interface. The authors believed that progressive ectatic

257 changes in the host collagen might pull the graft DM mechanically, thereby

258 leading to spontaneous DM detachment.26

259 Ho and coworkers described spontaneous DMD or DM dehiscence following

260 PK in two cases arising from the graft–host interface.29 One case was a large

261 inferonasal DMD five months after regrafting that resolved after

262 descemetopexy. This was attributed to a slight decenetration of the donor

263 during trephination including a very peripheral segment of DM. Since, DM

264 tapers progressively from 7–10 µm to 0.5 µm at its periphery, it may be more

265 susceptible to tears. A second case was an inferotemporal DM dehiscence

266 with sub-epithelial haze one-month post PK for advanced keratoconus that

267 resolved spontaneously, but with persistent corneal edema. This might be due

11
268 to the thinning of peripheral DM together with corneal ectasia and changes in

269 the DSI leading to spontaneous DM dehiscence at the graft–host interface.29

270 Lin and coworkers reported a case of late spontaneous large DMD in

271 recurrent pellucid marginal degeneration after PK.47 The patient underwent

272 DSAEK following two failed attempts of descemetopexy. The mechanism is

273 related to the different tolerance to stretch of corneal stroma and Descemet

274 membrane as recurrent ectasia occurs in the graft.47

275 Another mechanism leading to DMD post keratoplasty includes inadvertent

276 injection of fluid at the graft-host junction leading to the direction of fluid jet

277 towards the graft. Moreover, patients with congenital hereditary endothelial

278 dystrophy are prone to a double anterior chamber as the result of the

279 presence of a thick posterior collagen layer of the DM leading to retention of

280 host DM during PK.

281 6.2.1. Post Deep Anterior Lamellar Keratoplasty (DALK) DMD

282 Lin and coworkers also reported a case of post DALK DMD in a case of

283 healed viral keratitis with anterior stromal scarring.48 Descemetopexy with air

284 injection was done on day 2, following which a shallow DMD persisted. At 5

285 months follow-up a complete resolution of DMD with a clear graft was noted.

286 DMD post DALK is attributed to micro or macro-perforations during host

287 dissection or due to retained DM and functional endothelium of the donor

288 cornea.48

289 Mechanism for spontaneous resolution hypothesized was that the sandwiched

290 endothelium might act as “pumps” that could possibly gradually expel the

291 aqueous between the graft–host interface.48 One pump is at the entrance, and

292 the other is at the exit of the “detachment pool,” thereby, leading to the

12
293 formation of a stable “second anterior chamber” and maintaining the

294 transparency of cornea. Subsequently, the “detachment pool” dries up and

295 reattachment of DM may occur when the donor endothelial cells (entrance

296 pump) die or lose their function. The death of donor endothelial cells may be

297 either from the mechanical friction between donor and host or from the

298 accumulation of metabolic waste and lack of nutrients between the graft–host

299 interface.

300 Post DALK DMD has also been reported in cases undergoing big-bubble

301 DALK as the result of an unrecognized type 2 bubble during the procedure.37

302 This has been described by Jinagal and coworkers as a hyperreflective

303 membrane in the anterior chamber extending from one peripheral lip to the

304 other of the host cornea in a case of spheroidal degeneration with anterior

305 stromal opacity undergoing DALK.37 This was associated with graft edema

306 and decreased vision postoperatively; however, it attached spontaneously

307 after reabsorption of air bubble, resulting in a clear graft at follow-up.

308 It is well known that three types of big bubbles (BB) can be achieved on air

309 injection into the corneal stroma during DALK.61 1) Type 1 BB is formed

310 between the Dua layer (DL) and the deep stroma. It is central with a white

311 margin and measures around 8 to 9 mm in diameter and is the preferred type,

312 as DL confers additional strength to the recipient cornea. 2) Type 2 BB is

313 formed between the DM and the posterior surface of DL. This is larger in size

314 with a clear margin and more susceptible to tears. 3) Mixed BB is formed

315 when the above two coexist, usually type 1 is complete and type 2 is partial.18

316 Thus, DMD post DALK can occur due to retained or unrecognized type 2 BB

317 in these cases which is seen as a pseudo anterior chamber filled with air and

13
318 DMD. It usually attaches spontaneously after the resorption of the air. The

319 retained type 2 BB can be easily recognized using intraoperative anterior

320 segment OCT during DALK.

321 Sharma and coworkers have reported DMD in a case of chemical injury with

322 corneal scarring who underwent manual DALK.68 There was a large DMD

323 extending from limbus to limbus in the central cornea that resolved with

324 descemetopexy and interface fluid drainage under the guidance of continuous

325 intraoperative anterior segment OCT.68

326 6.2.2. Symptoms

327 Patients with DMD after PK often presents with sudden diminution of vision if

328 the visual axis is involved, redness, a foreign body sensation, and haze

329 located around the area of DMD.26,29,47

330 6.2.3. Signs

331 Examination of these cases often reveals perilimbal conjunctival injection,

332 stromal edema with microcystic epithelial edema or bullae, with DM

333 detachment visible. There is no evidence of anterior chamber inflammation,

334 rejection, or keratitic precipitates, differentiating DMD from graft rejection. The

335 most common site of DMD reported in cases of cornea ectasia is the inferior

336 or temporal graft host junction, mostly associated with graft ectasia or

337 recurrence of the primary disease in the graft. Anterior segment OCT is used

338 to confirm and to locate the extent of DMD. Endothelial count on specular

339 microscopy is reduced.26,29,47

340 Miscellaneous

341 6.3. Following glaucoma surgeries

14
342 DMD has been reported after trabeculectomy by several authors, which

343 usually required multiple injections of gas tamponade for resolution.67

344 Management of DMD after trabeculectomy is quite challenging as compared

345 to that after cataract surgery. Since the eye after trabeculectomy is no longer

346 a closed system, the tamponading agents have a tendency to escape through

347 the ostium, which explains the multiple interventions required.

348 Predisposing factors include accidental insertion of the instruments between

349 stroma and DM, blunt keratomes, shallow anterior chamber, and inadvertent

350 injection of saline or viscoelastic between the deep stroma and DM. In

351 addition, preexisting DSI abnormalities or weak adhesions between them may

352 also play an important role.67

353 Sharifipour and coworkers reported a case of total DMD after trabeculectomy

354 along with choroidal effusion. Two attempts of intracameral air injection failed;

355 however, DMD resolved with transconjunctival closure of the scleral flap with

356 10/0 nylon sutures, choroidal tap, and intracameral injection of 20% sulfur

357 hexafluoride.67

358 Sluch and coworkers described a case of hemorrhagic DMD post

359 canaloplasty.73 This large inferonasal DMD developed from viscoelastic

360 injection into the Schlemm canal done in order to break the obstruction.

361 Subsequently, a saline wash and placement of an air bubble helped to resolve

362 the DMD.73

363 Following chemical injury

364 Various authors have reported DMD in cases of chemical injury (mostly

365 alkaline in nature) in around seven cases.31,59,82–84 The onset of DMD varies

366 from 3 days to 4 months with the most common site being the inferior half (the

15
367 inflammatory cells and fibrinous exudates gravitate down in the inferior

368 anterior chamber). 4/7 cases underwent intracameral gas injection out of

369 which two-showed reattachment of the DM. Resolution of post-chemical injury

370 DMD has been reported in early onset cases (the result of loose DMD) with

371 20% SF6 intracameral injection or even spontaneously.83,84,82

372 The late onset cases were associated with thick detached DM that was

373 fibrosed and adherent to the underlying iris tissue suggesting a tractional

374 cause for DMD. Other mechanisms proposed include severe cellular damage

375 in the stroma and endothelial layer, formation of an inflammatory retrocorneal

376 membrane associated with an organizing hyphema thereby pulling the DM or

377 this retrocorneal membrane develops neovascularization that ruptures and

378 fills the space between DM and stroma leading to hemorrhagic DMD.84

379 Following birth trauma

380 DM tears after forceps injuries occur, but DMD has been described rarely.2,44

381 These tears are attributed to compression of the globe against the orbital roof

382 by a forceps blade slipping over the inferior orbital edge and thus are typically

383 vertical and linear (the result of horizontal stretching), single or multiple, and

384 associated with corneal astigmatism, amblyopia, and high myopia.2,44,49

385 Kancherla and coworkers reported a case of DMD in a 3-day-old infant from

386 forceps-related birth injury.40 Examination under anesthesia using high-

387 frequency ultrasound and handheld OCT revealed a linear tear in DM

388 superiorly, with DMD extending nasally and temporally. This was managed

389 with intracameral air injection, superior peripheral iridectomy, and penetration

390 of the overlying cornea with the needle of a 10-0 nylon suture and release of

391 clear viscous fluid, leading to apposition of DM.40

16
392 6.4. Following syphilitic interstitial keratitis

393 Hollhumer and coworkers described a case of hemorrhagic DMD as a late

394 complication of syphilitic interstitial keratitis in a 65-year-old woman with

395 congenital syphilis.30 The patient had progressive shallowing of the anterior

396 chamber from a hemorrhagic DMD, along with corneal neo- vascularization

397 and a positive syphilis serology. This was managed with surgical drainage of

398 the blood via an ab externo approach (because of the risk of pupillary block

399 glaucoma), that is, making a clear corneal incision into the hematoma and

400 washing of the interface with balanced salt solution washout along with an

401 anterior chamber air tamponade to prevent further bleeding and facilitate

402 reattachment of DM.30

403 6.5. Following radial keratotomy

404 DMD has been described 20 years after radial keratotomy (RK, 16 cuts) in a

405 43-year-old man who presented with gradually progressive diminution of

406 vision over six months.64 Detailed examination and ASOCT showed a large

407 DMD with severe corneal edema mostly involving inferior half of cornea. The

408 patient was tentatively scheduled for DSAEK and started on topical hypertonic

409 solution four times a day. Eight months later there was a significant

410 improvement in the visual acuity along with reduction in corneal thickness

411 from 891 to 630 µm and spontaneous resolution of the DMD.64

412 RK has known to cause endothelial damage and corneal decompensation;39

413 however, a few studies have shown stabilization of endothelial cell count and

414 a reduction in the rate of endothelial cell loss from 3.3% to 0.4% every year at

415 7-year follow-up.53,79 Rosetta and coworkers hypothesized that corneal

416 decompensation; later might develop as a result of DMD that originated under

17
417 the corneal dialysis through RK incisions.64 The fluid accumulation the stroma

418 might be caused by an osmotic flow and later extended without any further

419 endothelial loss. Thus, topical hypertonic drops may have acted by reversing

420 the osmotic flow, leading to progressive absorption of the fluid and attachment

421 of the DM.64

422 7. Classification

423 Several authors have classified DMD depending upon its configuration,

424 height, extent, length and position with respect to pupil (Table 2).

425 7.1. Samuel classification

426 Samuels and coworkers classified DMD’s into 3 types namely, active (pushed

427 back), passive (pulled back or torn away) and detachments because of

428 difference in elasticity between the parenchyma and the glass membrane

429 causing DM to roll on itself or form folds.65 Active detachments occur due to

430 active exudation between the corneal lamellae and Descemet membrane

431 pushing the DM backward while passive detachments occur when exudates in

432 anterior chamber organize and contract drawing the Descemet membrane

433 away from the lamellae.

434 7.2. Mackool classification

435 Mackool and coworkers classified DMDs into 2 broad types, planar and non-

436 planar.52 When the separation between Descemet membrane from its

437 overlying stroma is less than 1mm in all areas, it is called planar, whereas

438 when the separation is greater than 1mm in any area, it is considered as non-

439 planar. Both planar and non-planar detachments are further subdivided into

440 peripheral detachments (of the peripheral 3 mm) and combined peripheral

18
441 and central detachments. This classification highlighted a better prognosis of

442 planar DMDs even without surgical repair.

443 7.3. Jain classification

444 Jain and coworkers classified DMDs into three groups based on the extension

445 of detachment as mild, moderate or severe.35 Mild DMDs involve less than

446 25% of the cornea and are peripheral, moderate DMDs involve 25–50%

447 cornea and are peripheral and severe DMDs involve more than 50% of the

448 cornea or involve the central cornea. They studied the anatomic and visual

449 outcomes of descemetopexy in DMD after cataract surgery. Better anatomical

450 and functional outcomes were noted with air as compared to C3F8 along with

451 no reports of pupillary block with air. The predictors of poor visual outcome

452 were identified as patients with advanced cataract, prolonged duration

453 between cataract surgery and descemetopexy and cataract with corneal

454 opacity.

455 7.4. Jacob classification

456 Jacob and coworkers developed a classification of DMDs based on the

457 etiology, clinical features, anterior segment optical coherence tomography

458 (ASOCT) findings, intraoperative features, and management protocol.33 They

459 classified DMDs into 4 broad groups namely rhegmatogenous Descemet

460 detachment (RDD), tractional Descemet detachment (TDD), bullous

461 Descemet detachment (BDD) and complex Descemet detachment (CDD).

462 RDD is characterized by a lax, free floating DM secondary to tear, hole or

463 dialysis of DM at Schwalbe line. It is the most common type, occurring post-

464 surgery in case of use of blunt instruments, holes due to micro perforation in

465 deep anterior lamellar keratoplasty (DALK) or as complication of

19
466 trabeculectomy and trabeculotomy. On ASOCT, DM is seen as an undulating

467 linear hyperreflective signal in the anterior chamber with the overlying stromal

468 arc length similar to the total length of the detached DM. Peripheral, planar

469 RDDs can be observed, while others are managed with

470 pneumdescemetopexy with air (superior detachments) or non-expansile

471 concentration of 20% SF6 (inferior/recurrent detachments) along with

472 internal/external supra-Descemetic fluid drainage.

473 TDD is characterized by a foreshortened, stretched out taut DM with tractional

474 / fibrotic component. Traction occurs secondary to inflammation / fibrosis /

475 incarceration in wound / graft-host junction/peripheral anterior synechiae /

476 suture. On ASOCT, TDD is seen as a straight taut linear signal. The arc

477 length of the overlying cornea is greater than the chord length of the detached

478 DM. They are managed by relaxing descemetotomy till the DM is fully

479 opposed to the stroma.

480 A smooth bulge of DM into AC characterizes BDD in the absence of any DM

481 break or with a needle puncture break. It is usually seen post cataract or

482 viscocanalostomy surgery due to introduction of a viscous fluid

483 (viscoelastic/air/blood) in the supra-Descemet space. On ASOCT, BDD is

484 seen as a convex hyper-reflective signal and can be observed for

485 spontaneous absorption of fluid or intra-operative drainage can be performed

486 by applying a nick or post-operatively by YAG descemeto-puncture.

487 CDD is characterized by DM macrofolds / rolls / scrolled edges as well as a

488 combination of other variants of DD. They are usually seen post DMEK or

489 after poorly repositioned RDDs. On ASOCT, crumpled folds and scrolls may

490 be seen. Management varies and depends on the cause and extent of

20
491 detachment. This etiomorphological classification allows a systematic

492 approach for diagnosis, management and prognostication of different types of

493 DMDs.

494 7.5. HELP Algorithm

495 Kumar and coworkers proposed HELP algorithm; using the height, extent,

496 chord length, and relation to the pupil () based on ASOCT for the

497 management of post phacoemulsification DMD.42 Height is measured as the

498 distance between the detached DM and corneal stroma in micrometers. It is

499 classified as less than 100 µm, 100–300 µm, and more than 300 µm. Chord

500 length is the total length of detached Descemet membrane measured using

501 calipers in the analysis tool in ASOCT. It is further classified as length less

502 than 1 µm, 1–2 µm, and more than 2 µm. The cornea is classified into 3 zones

503 to analyze the extent of detachment, zone 1 (central)- 5mm, zone 2

504 (paracentral)- 5-8mm and zone 3 (peripheral)- >8mm. Position of the DMD

505 with respect to anatomical pupil size of specific patient is also noted. Based

506 on these 4 parameters, patients were either managed medically or surgically.

507 Medical management was done for patients with DMD with length less than

508 1mm and height < 100 microns in any zone, DMD with length 1-2mm and

509 height 100-300 m in zone 2 and 3 and DMD with length >2mm and height

510 >300 microns in zone 3. Surgical intervention consisted of intracameral

511 injection of 14% C3F8 or 20% SF6 or sterile air injection and was undertaken

512 in DMD with length 1-2mm with height of 100-300 microns in zone 1 (for both

513 with and without pupillary axis involvement) and DMD >2mm and height >300

514 microns in zone 1 & 2. Surgical intervention was also done in cases with no

515 resolution at 4 weeks with medical management.

21
516 This ASOCT based HELP algorithm is effective for managing post-surgical

517 DMD in eyes with dense corneal edema. Early surgical intervention for

518 detachments involving central cornea can prevent functional visual loss.

519 7.6. ASOCT based classification

520 Sharma and coworkers proposed an ASOCT based management algorithm

521 for the management of DMD causing persistent corneal edema (>2 weeks).71

522 The surgical plan of management was decided based on the configuration

523 (planar or scrolled) and location of DMD (Figure 2a, 2b, 2c, 2d). DMDs in the

524 superior half of the cornea with a planar configuration alone are managed

525 using intracameral air, and those with scrolled edges are managed using

526 intracameral 14% C3F8. DMDs involving inferior half of the cornea with planar

527 or scrolled edges are managed using intracameral C3F8 injection. DMDs with

528 extensive corneal involvement are also managed using intracameral C3F8.

529 This algorithm signifies the role of ASOCT for timely diagnosis,

530 characterization, and management of DMD in cases of non-resolving

531 postoperative corneal edema.

532 8. Investigations

533 The preoperative investigations in a case of DMD are required to plan for the

534 management of these cases.

535 8.1. Anterior segment optical coherence tomography

536 ASOCT is very useful in the diagnosis, treatment, and monitoring of various

537 anterior segment disorders. The principle is based on the optical scattering of

538 different ocular tissue structures, using interferometry for two-dimensional

539 imaging and quantitative analysis. It provides high-resolution cross-sectional

540 images of the anterior segment even through a relatively opaque cornea, and

22
541 minimal experience is required for image acquisition, hence making it an

542 indispensable tool in corneal disorders. Using ASOCT, DMD can be classified

543 into various categories as described above (Figure 2a, 2b, 2c, 2d). This

544 categorization further aids in deciding the management plan for these cases.

545 8.1.1. ASOCT-based classification

546 Jacob and coworkers and Sharma and coworkers have classified DMD using

547 ASOCT findings, which has been described in detail in the classification

548 section.33,71

549 8.1.2. ASOCT-based management

550 Main parameters taken for DM detachment (DMD) are obtained from ASOCT.

551 Kumar et al proposed HELP (height-, extent-, length-, and pupil-based)

552 treatment protocol for DMD.42 This has been described in the above section.

553 8.2. Ultrasound biomicroscopy (UBM)

554 Ultrasound biomicroscopy (UBM) is also a useful tool in visualizing and

555 locating DMD along with guiding surgical repair, particularly in hazy media,

556 which impedes satisfactory visualization using slit lamp and gonioscopy.8

557 Major limitations include requirement of a skilled technician, a co-operative

558 patient, and it is a time consuming procedure.58 Radhakrishnan and

559 coworkers assessed the accuracy of ASOCT versus UBM to identify narrow

560 angles with image-derived anterior chamber angle parameters.62 Although

561 both had similar reproducibility, sensitivity and specificity, ASOCT was found

562 to be superior to UBM since it provides high-resolution images and can

563 accommodate multiple angles of incidence to the tissues, whereas UBM gives

564 the best reflectance and, therefore, signal when the tissue planes are

565 perpendicular to the sound energy. Moreover, it is a non-contact procedure,

23
566 has a high speed, and easily acquires images even in upright position. Winn

567 and cowokers compared ASOCT versus UBM in DMDs before surgical repair

568 and concluded that the image quality of ASOCT was superior and also the

569 absence of corneal contact reduces the risk of infection.81

570 8.3. Gonioscopy in DMD

571 Gonioscopy improves the accuracy of diagnosis in cases of small and

572 peripheral DMDs, however severe corneal edema frequently limits its use.57

573 9. Management

574 The management of DMD needs a case based approach. It is important to

575 decide early in the course whether to manage the case conservatively with

576 medication or to intervene surgically to have the best visual outcome. The

577 sites, extent, height of DMD along with the presence of any scrolled edges are

578 few important parameters that should be considered while making this

579 decision.3,42

580 9.1. Conservative management

581 Various authors have suggested spontaneous reattachment of the detached

582 DM with conservative management.42,52 This is most often seen in cases with

583 small, peripheral, planar DMD with non-scrolled edges.52 Conservative

584 therapy constitutes of topical steroids and hyperosmotic agents (hypertonic

585 saline 5% drops, hypertonic saline 6% ointment). Steroids help in controlling

586 the inflammation and reduce the risk of developing DM fibrosis and scar.

587 Hypertonic agents imbibe fluid from the corneal stroma and helps in

588 dehydrating the cornea. This results in clearing of the corneal edema,

589 improving the corneal clarity and transiently improving the visual acuity.

590 Whether the use of hyperosmotic agent has any role in improving the

24
591 attachment of the detached DM to the stroma is questionable and needs

592 further research.

593 Mackool and coworkers suggested that cases with planar DMD respond well

594 to medical therapy.52 They observed that spontaneous reattachment of the

595 DMD with conservative management in three of the four cases of planar

596 DMD, but in only one of the five cases of non-planar DMD. Similarly, Sharma

597 and coworkers reported spontaneous resolution of DMD in all cases of post

598 cataract surgery planar DMD (N=14) with conservative management.70

599 Assia and coworkers reported spontaneous reattachment of the DM with

600 conservative therapy in five cases of subtotal DMD without rolled scrolls at

601 two to three months follow up.3 They concluded that even cases of non-planar

602 DMD with non-rolled scrolls respond well to conservative treatment with

603 topical steroids and hyperosmotic agents.

604 Kumar and coworkers suggested an ASOCT-based HELP algorithm to

605 ascertain the management of cases with DMD.42 The authors suggested

606 conservative management in all cases with DMD height <100 micron and

607 length <1 mm, DMD height 100-300 microns and length 1-2 mm that is not

608 involving the pupil and, DMD with height >300 micron and length >2mm in

609 zone 3 (beyond 8 mm of the central cornea). In a prospective comparative

610 study (n=116) following the HELP algorithm, wherein one group underwent

611 surgical intervention and the other was managed conservatively, the authors

612 reported a success rate of 96.9% in cases undergoing conservative

613 management (n=65). Cases that did not show spontaneous reattachment by 4

614 weeks were taken up for surgical intervention. The authors observed no

25
615 difference in the final corrected distance visual acuity between the two

616 groups.42

617 9.2. Surgical management

618 9.2.1. Indication

619 Surgical intervention results in rapid visual recovery, reduces the risk of

620 corneal complication and need for future keratoplasty. All cases of DMD do

621 not warrant surgical intervention, and in specific conditions DMD can be

622 carefully observed for spontaneous re-attachment of DM. Surgical intervention

623 as the primary treatment for DMD is suggested for cases with non-planar

624 DMD, scrolled edge, length of DMD >2mm or involving the central

625 cornea.3,42,52 In addition, all cases of DMD that are non-resolving with

626 conservative therapy require surgical intervention (Table 3).

627 Mackool and coworkers reported that only one of the five cases of non-planar

628 DMD that was managed conservatively showed spontaneous re-attachment

629 of DM, while six of the eight cases of non-planar DMD that underwent surgical

630 management showed reattachment of DM, suggesting the requirement for

631 surgical intervention in cases of non-planar DMD (Figure 2a, 2b, 2c, 2d).52

632 Kumar and coworkers in the HELP algorithm suggested surgical management

633 in cases of DMD with length 1-2 mm and height 100-300 micron in the central

634 5 mm of the cornea and, length > 2mm and height >300 micron in the central

635 8 mm of the cornea at presentation.42 They also suggested surgical

636 management in all cases of non-resolving DMD at 4 weeks follow-up.

637 Marcon and coworkers in a retrospective case series (n=15), reported

638 resolution in 8 cases with medical therapy alone with a mean time to

639 resolution of 9.8 weeks.54 One case in the medical therapy group showed

26
640 failure to therapy and required keratoplasty. Intracameral SF6 was injected in

641 five patients with successful outcome in three cases. One case required a

642 repeat injection and another required keratoplasty. The authors concluded

643 that medical therapy alone may be adequate in most of the cases and should

644 be the initial treatment of choice.54

645 9.2.2. Descemetopexy

646 Sparks and coworkers first used the term “descemetopexy” in 1967 to

647 describe the surgical reattachment of detached DM with injection of air into

648 the anterior chamber in three cases of post cataract surgery DMD.75 Since

649 then, descemetopexy has become the gold standard treatment for the

650 management of DMD. The rapid absorption of 100% air from the anterior

651 chamber led to the concept of using isoexpansile gases,--2-14% per-

652 fluoropropane (C3F8) and 14-20% sulphur hexafloride (SF6)--that would stay

653 in the anterior chamber for longer time (14% C3F8- 6 weeks; 20% SF6- 2

654 weeks).19,41,68 Isoexpansile gas reduces the need for repeat injections. The

655 surgical technique involves filling the syringe with the desired gas, which is

656 aspirated through a micropore filter. An anterior-chamber paracentesis is then

657 made with a micro vitreoretinal blade or the gas is injected with a 26 or 30-

658 gauge needle.54 The site of entry chosen should be opposite to or away from

659 the area of the DMD where the DM is attached. Once adequate aqueous is

660 ejected, a continuous, single bubble of the gas is injected into the anterior

661 chamber directing towards the maximum height of DMD. A complete gas-filled

662 chamber is maintained for at least 15-20 minutes.60 Thereafter, 1/3rd bubble

663 can be released depending upon the surgeon’s choice, and the size of gas is

664 then reduced to two-third of anterior chamber or 8 mm bubble size to avoid

27
665 post-operative pupillary block. It is advisable to perform an inferior peripheral

666 iridectomy if a complete bubble is left in anterior chamber. It is important for

667 the patient to maintain supine position after the procedure. Also, some prefer

668 the use of cycloplegic drops and pre-operative laser peripheral iridotomy to

669 prevent this complication.12 The side-port entry is then hydrated or sutured

670 with a 10-0 monofilament nylon suture.

671 This procedure be associated with a risk of raised intraocular pressure and

672 pupillary block glaucoma (11.6%)35,34,42 Descemetopexy involving injection of

673 large amount of air or gas can lead to compression of iris against the lens

674 surface leading to iris ischemia and subsequent Urrets-Zavalia syndrome.56

675 This has been reported in cases of post DALK DMD in patients with

676 keratoconus.56 Performing an inferior peripheral iridectomy during

677 descemetopexy and avoiding administration of mydriatics in patients with

678 keratoconus post keratoplasty can prevent this complication.

679 Few authors have also reported endothelial dysfunction with the use of iso-

680 expansile SF6 and C3F8 in animal studies; however, there are no human

681 studies to validate these results.22,45,46 Drainage of pre-descemetic fluid is

682 performed in selected cases by stab incision on the cornea or needle

683 aspiration of the fluid to achieve better attachment.6

684 Sharma et al in an ASOCT based algorithm for management of cases with

685 persistent corneal edema following intra-ocular surgery, clearly defined the

686 indication for use of air and isoexpansile gas.71 The authors suggested

687 intracameral injection of air for all cases of planar DMD involving the superior

688 half of the cornea. Intracameral injection of isoexpansile per-fluoropropane

689 was recommended for cases with DMD involving the inferior half of the cornea

28
690 and superior DMD with scrolled edges. Successful descemetopexy was

691 achieved in all cases (n=25) with requirement for repeat injection of

692 perfluoropropane in one case. Raised intra-ocular pressure was noted in two

693 cases of per-fluoropropane group. The mean time for resolution of DMD was

694 16.0±7.1 days in this study.71

695 Chaurasia and coworkers reported successful descemetopexy with air in 13 of

696 the 14 cases of DMD.10 Eight cases showed clinical resolution at one-week

697 follow-up, while all cases resolved at 4-6 weeks follow-up. Failure was noted

698 in one case due to presence of fixed folds in the DM.

699 Jain and coworkers, in a retrospective case series (n=60), reported 95%

700 success rate with pneumatic descemetopexy in cases of post-cataract surgery

701 DMD.34 There was no difference in the success rate between intracameral air

702 (n=24) and 14% C3F8 injection (n=36). Keratoplasty was eventually required

703 in 5% cases that had treatment failure. Pupillary block glaucoma was

704 observed in 11.6% (n=7) cases of C3F8 injection, while none of the cases of

705 intracameral air injection developed a similar complication. The authors

706 concluded that air has better efficacy with less risk of post-operative

707 complication and hence should be preferred.

708 Garg and coworkers in a retrospective case series (n=67), reported the

709 outcome of intracameral C3F8 for the management of post cataract surgery

710 DMD.24 Complete re-attachment of DM was noted in 72% of the cases and

711 partial re-attachment in 18% of the cases. Success rate was higher in cases

712 with planar DMD compared to non-planar DMD. Also, the authors observed

713 that the time to intervention from cataract surgery had a significant impact on

714 the management outcome. Failure of the DM to re-attach was noted in 87.5%

29
715 of the cases that had an interim period >3 months following cataract surgery.

716 Post-operative pupillary block and raised IOP was observed in 13.4% of the

717 cases.24

718 Odayappan and cowokers in a retrospective case series (n=112) of post-

719 cataract surgery DMD managed with air descemetopexy, reported successful

720 re-attachment with primary descemetopexy in 71% cases.60 Repeat

721 descemetopexy was performed in 15 cases with successful re-attachment in

722 60% cases. Visual acuity was > 6/18 in 75% cases at 1 month follow-up.

723 Persistent DMD (21.8%), corneal decompensation (7.3%), appositional angle

724 closure (18%), pupillary block with air (2.7%) and uveitis (2.7%) were the

725 post-operative complications noted in this study. The mean interval between

726 the first and second intervention was 5.1 ± 3.1 days. A success rate of 92.3%

727 was observed in this study with significant. One case had persistent DMD

728 even after second intervention and subsequently underwent endothelial

729 keratoplasty. The authors reported the use of same gas, as used in the

730 primary intervention, in nine patients (air- 4; C3F8- 5). C3F8 was used

731 following air in four patients. No difference was observed in the re-attachment

732 rate between air and C3F8. However pupillary block glaucoma was observed

733 in one case of C3F8 injection.60 Jain et al reported a similar success rate

734 (92.3%) for repeat pneumatic descemetopexy for cases with persistent

735 DMD.34 Hence, repeat descemetopexy can be attempted in cases with failed

736 primary descemetopexy before proceeding for complex surgical procedure

737 like endothelial keratoplasty.

738 9.2.3. Mechanical tamponade

30
739 Donzis and coworkers in 1986 first reported the surgical repair of DMD with

740 intracameral injection of sodium hyaluronate (Healon®).16 The authors

741 reported that the viscoelastic property of sodium hyaluronate helps to move

742 the DM to its appropriate position following intracameral injection.

743 Subsequently, few authors have reported its use in cases of DMD with

744 scrolled edge and extensive DMD following a failed primary pneumatic

745 descemetopexy.5,74 Intracameral injection of perfloro-n-octane has also been

746 described in literature for management of persistent DMD.43 However, most of

747 these are isolated case reports and there are no large studies to report its

748 outcome. Therefore, its use is largely limited to cases with recalcitrant DMD,

749 wherein the primary attempt of pneumatic descemetopexy has failed. All

750 cases of DMD undergoing mechanical tamponade of the DM with sodium

751 hyaluronate should be prescribed with prophylactic anti-glaucoma medication

752 to control the expected post-operative IOP spike in these cases.

753 9.2.4. Suture fixation

754 Various authors have described the use of 10-0 monofilament nylon suture for

755 trans-corneal suture fixation of DMD with variable success.1,4,5,12,36 It is usually

756 combined with intracameral injection of air or gas. The disadvantage

757 associated with trans-corneal fixation of the DMD is the risk of tenting of the

758 Descemet membrane, like a taut chord under the corneal arc, at the site of

759 origin of DMD. Also, there is risk of progression of the DMD, as the leading

760 edge is not secured. Therefore, this procedure is preferred in cases of large

761 and intractable DMD.1

762 9.2.5. Manual Repositioning

31
763 Manual repositioning of the DM in cases of DMD is now considered an

764 obsolete procedure with limited reports in literature to support its use. Das and

765 coworkers and Sparks and coworkers described the use of this procedure for

766 cases of DMD with scrolled edges.13,75 An iris spatula or a cyclodialysis

767 spatula have been used for repositioning of the DM. Manual repositioning of

768 the DM is followed by intracameral injection of air or gas for tamponade.

769 9.2.6. Descemetotomy

770 The term descemetotomy was coined by Lowenstein and coworkrs in 1993 for

771 management of post-keratoplasty cases with retained host descemet

772 membrane.50,51 It consists of either surgical removal of the membrane or

773 creation of breaks in the host DM with the help of Nd-YAG laser.11,55 Relaxing

774 descemetotomy is different from descemetotomy, and is performed for cases

775 with a taut DM as seen in cases of tractional DMD.33 It can also be performed

776 in cases with bullous DMD wherein there is no break in the detachment DM to

777 allow drainage of the supra-descemetic fluid. Jacob and coworkers described

778 the technique of “ab externo relaxing descemetotomy” for bullous DMD.32 In

779 this technique, a clear corneal incision, close to the limbus, is made with a

780 keratome, which is carefully advanced inwards into the anterior chamber to

781 incise the taut DM. This is followed by pneumodescemetopexy to allow

782 internal drainage of the supra-descemetic fluid into the anterior chamber.

783 Jacob and coworkers reported successful outcome with this technique in

784 three cases of bullous DMD that had failure of primary

785 pneumodescemetopexy. In another case series, the same author reported

786 successful outcome of relaxing descemetotomy in cases with tractional

787 DMD.33 Asymptomatic peripheral corneal scar was observed in two cases;

32
788 however, one case had corneal opacity in the area of absent DM. Rathi and

789 coworkers reported the successful management of a case of late onset

790 spontaneous DMD post cataract surgery with Nd:YAG laser

791 descemetotomy.63 Complete clearing of cornea was noted at two weeks

792 follow-up with minimal corneal scarring at the site of laser application;

793 however, it is important to note that the procedure of relaxing descemetotomy

794 is itself fraught with the risk of corneal endothelial damage and hence should

795 be avoided in asymptomatic cases with small peripheral DMD.

796 9.2.7. Interface Drainage

797 Drainage of interface fluid or supra-descemetic fluid is usually performed in

798 combination with pneumodescemetopexy in cases with primary failure of

799 pneumodescemetopexy. Authors have described the use of 20-gauge micro-

800 vitreoretinal blade, 23-gauge needle and curved needle of 10-0 monofilament

801 suture for draining the supra-descemetic fluid from the interface with good

802 outcomes.6,25,72,80

803 Singh and coworkers reported the use of intra-operative optical coherence

804 tomography (iOCT) for intra-operative visualization of DM attachment.72 The

805 use of iOCT, if available, for management of cases of DMD can be useful in

806 intra-operative visualization of the DMD and assessment of DM re-attachment

807 at the end of procedure. This can help to reduce the intra-operative surgical

808 manipulation as well as total surgical time.

809 9.2.8. Keratoplasty

810 Keratoplasty is the last treatment option reserved for cases of recalcitrant

811 DMD wherein other treatment options have failed. Endothelial keratoplasty in

812 the form of Descemet stripping automated endothelial keratoplasty (DSAEK)

33
813 and Descemet membrane endothelial transplant is preferred for the

814 management of cases of corneal edema with DMD.34,60 However, in long

815 standing cases of DMD with corneal edema and scarring often require

816 penetrating keratoplasty for visual rehabilitation. Odayappan and coworkers,in

817 a retrospective case series (n=112) of post cataract surgery DMD, reported

818 requirement for DSAEK in 7.3% cases following failure of pneumatic

819 descemetopexy.60 Most of these cases had either a large DM tear or areas of

820 missing DM that resulted in corneal decompensation. In another case series

821 (n-13), the authors reported the need for endothelial keratoplasty in a case of

822 persistent DMD following repeated pneumatic descemetopexy.34

823 To conclude, a case based approach is required for management of cases

824 with DMD. Good visual outcome can be obtained with early intervention in

825 these cases. Pneumatic descemetopexy is the gold standard treatment for

826 management of most of the cases. Other treatment options are often used in

827 cases that fail to respond to pneumatic descemetopexy with keratoplasty is

828 kept reserved as the treatment option in these cases.

829 9.3 Management of post keratoplasty DMD

830 As discussed in the above sections, DMD may occur after both PK and DALK.

831 It has been seen to occur at the graft-host junction or at peripheral host area

832 mostly in cases of corneal ectasia.26,29,47 Various management options

833 described in literature include descemetopexy, interface fluid drainage and

834 DSAEK. 26,29,47,17,78 Spontaneous resolution of DMD has been described after

835 DALK in cases with retained donor endothelium.48

836 Descemetopexy is the most commonly performed procedure for management

837 of DMD even after keratoplasty; however, some of the cases might require

34
838 drainage of interface fluid or retained viscoelastic. This has been described by

839 Sharma and coworkers under the guidance of continuous intraoperative

840 ASOCT68 The interface fluid can be released from the anterior surface

841 through the graft host junction in cases of post DALK DMD. Post DALK DMD

842 can also occur due to the presence of interface air bubble. This can be

843 managed by the technique of “reverse double bubble” as described by Titiyal

844 and coworkers.78 This technique was used in a case of total DMD with air

845 bubble in the interface noted on the first postoperative day following DALK for

846 healed keratitis. This involves injection of intracameral air via a 30-gauge

847 needle through a partial thickness MVR entry at the posterior limbus, leading

848 to the movement of the interface bubble towards the center. The two distinct

849 air bubbles, one in interface and other in anterior chamber could be identified,

850 and the interface air bubble was removed by gently milking with an iris

851 repositor towards the end of surgery to achieve successful reattachment of

852 the DM.

853 10. Conclusions

854 DMD is an important cause of vision loss after any intraocular surgery

855 particularly cataract surgery if involving the visual axis and is extensive. The

856 management of DMD varies from case to case depending upon various

857 parameters. Spontaneous resolution is common in small, peripheral and

858 planar DMD’s, while large, central, non-planar, scrolled DMD’s require

859 surgical intervention. Prompt diagnosis and timely management of such cases

860 often lead to a good visual outcome. Various treatment options are available

861 but the optimal treatment depends upon the type and extent of DMD.

862 11. Future directions

35
863 The use of modern tools such as ASOCT and UBM can help in early

864 diagnosis and prompt management of DMD especially in cases with corneal

865 edema and difficult visualization to prevent long-term complications like

866 corneal decompensation and stromal scarring. Further, the management of

867 DMD has been revolutionized with the advent of intraoperative optical

868 coherence tomography that allows identification of correct plane of

869 instrumentation and real time monitoring of supra Descemet membrane fluid

870 removal if present along with reattachment of DM. This would help to improve

871 the surgical precision leading to a better anatomical and functional outcome.

872 Further, prospective and comparative trials are required to discover the best

873 possible treatment option for DMD.

874 12. Literature search

875 A literature search was performed using PubMed Medline, the Cochrane

876 Library Database, EMBASE and Scopus (from 1970 onwards), using the

877 following terms: Descemet membrane detachment, classification of DMD,

878 management of DMD, descemetopexy, DMD after cataract surgery, anatomy

879 of DM, risk factors of DMD, post keratoplasty DMD, ASOCT in DMD and UBM

880 for diagnosis of DMD. All relevant articles were included. Priority was given to

881 prospective studies and randomized clinical trials. However, retrospective

882 studies and case reports were included if important. Reference lists from the

883 selected articles were further checked to obtain further relevant articles not

884 included in the electronic database.

36
885 Abbreviations

886 DMD- Descemet membrane detachment

887 VA- Visual acuity

888 DSAEK- Descemet stripping endothelial keratoplasty

889 CDVA- Corrected distance visual acuity

890 ASOCT- Anterior segment optical coherence tomography

891 C3F8- Perfluoropropane

892 IOP- Intra-ocular pressure

893 SF6- Sulphur hexafluoride

894 EK- Endothelial keratoplasty

895 DM- Descemet membrane

896 HELP- Height-, extent-, length-, and pupil-based

897 UBM- Ultrasound biomicroscopy

37
898 Disclosure

899 The authors report no proprietary or commercial interest in any product

900 mentioned or concept discussed in this article. This research did not receive

901 any specific grant from funding agencies in the public, commercial, or not-for-

902 profit sectors.

903 Table legends

904 Table 1: Risk factors for descemet membrane detachment

905 Table 2: Classifications for descemet membrane detachment

906 Table 3: Management outcomes in descemet membrane detachment

907 Figure legends

908 Figure 1: Slit lamp photograph showing a central planar DMD associated with

909 stromal edema with DM folds

910 Figure 2: 2a &b; Preoperative and postoperative ASOCT image of a case with

911 a large DMD involving the central visual axis and managed with intracameral

912 SF6 injection

913 Figure 2c &d; Preoperative and postoperative ASOCT image of a case with

914 extensive DMD with scrolled edges involving the central visual axis and

915 managed with intracameral C3F8 injection

38
916 References
917
918 1. Amaral CE, Palay DA. Technique for repair of Descemet membrane
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1189

46
1190 Table 1: Risk factors for DMD
1191
Pre-operative Intra-operative Post-operative/
Delayed causes
Old age Clear corneal incision Factors for
(small, oblique, ragged) Spontaneous/
bilateral DMD
Dense cataract Blunt instrumentation Abnormality in DSI
Lack of adequate Inadvertent damage by Corneal ectatic
anaesthesia instruments disorders
Previous history of Total ultrasound time > Endothelial disorders
chemical injury 60 seconds like FECD
Corneal neovascularization

1192
1193 Footnotes: DMD- descemet membrane detcahment, FECD- Fuch’s
1194 endothelial corneal dystrophy, DSI- Descemet Stromal Interface
1195

1196 Table 2: Classifications of DMD

1197
1198 1. HELP algorithm for management of DMD42
1199
Medical Management Surgical Management
Extent Height Length Extent Height Length
Zone 1 <100 µ <1mm Zone 1 100-300 µ 1-2 mm
>300 µ >2mm
Zone 2 <100 µ <1mm Zone 2 >300 µ >2mm
100-300 µ 1-2 mm
Zone 3 <100 µ <1 mm
100-300 µ 1-2 mm

>300 µ >2 mm

1200

1201 2. ASOCT based management algorithm for DMD71

Location of DMD Configuration Management

Superior half of Planar edges Intracameral air

cornea Scrolled edges Intracameral C3F8
Inferior half of cornea Planar edges Intracameral C3F8

47
 Scrolled edges Intracameral C3F8
Extensive Intracameral C3F8
involvement of
cornea
1202

1203 Footnotes: DMD- Descemet membrane detcahment, C3F8-

1204 Perfluoropropane, HELP: Height extent length pupil based, ASOCT- Anterior
1205 segment optical coherence tomography
1206
1207
1208 Table 3: Management Outcomes in DMD
1209
Autho Study Sample Intervent Outcome Complica Clinical
r Type size ion tion Implicati
on
Odaya Retrosp Post- Air Successf Persistent Air
ppan ective cataract descemet ul re- DMD descemet
et al., case surgery opexy attachme (21.8%) opexy is
201860 series DMD n=112 nt after Corneal safe and
primary decompe effective
descemet nsation for
opexy (7.3%) manage
71%. Appositio ment of
15 nal angle DMD
patients closure
underwe (18%)
nt repeat Pupillary
descemet block with
opexy air (2.7%)
with 60% Uveitis
success (2.7%)
rate.
VA >6/18
in 75%
cases at
1 month
DSAEK-
7.3%
cases
Kumar Prospec Post Interventi Successf Pupillary ASOCT
et al., tive Phaco- on based ul block based
201542 case emulsific on HELP outcome glaucoma algorithm
series ation algorithm in 95.8% (7.7%) is
DMD cases of effective
Surgical surgical in
therapy therapy manage
n=96 and ment of

48
 Medical 96.9% cases
therapy cases of post-
n=65 medical surgical
therapy. DMD with
No severe
differenc corneal
e in oedema
CDVA
Sharm Prospec Post ASOCT Success Two C3F8
a et tive intra- guided rate was cases in should be
al., case ocular manage 100%. C3F8 preferred
201571 series surgery ment group had for
DMD algorithm raised inferior
N-37 IOP. One DMD and
case superior
required DMD with
repeat scrolled
injection edge
Jain et Retrosp Post Intracam Overall Pupillary Air is
al., ective cataract eral air success block better
201335 study surgery (n=24) rate was glaucoma than
DMD Intracam 95% with in 11.7% C3F8
N-60 eral no cases with less
C3F8 differenc intracame ocular
(n=36) e ral C3F8 complicat
between group ions
the
groups.
VA was
better in
the air
subgroup
Chaur Retrosp Post Intracam Success Raised Air can
asia et ective cataract eral air rate was IOP in be safely
al., study surgery 92.8%. 14.3% used for
201210 DMD VA was > cases pneumati
N-14 20/40 in c
11 cases descemet
opexy
Marco Retrosp Post Medical Successf One case
n et ective cataract therapy ul in each
al., case surgery (n=10) outcome group had
200254 series DMD Intracam in 90% treatment
N-15 eral SF6 cases of failure
(n=5) medical and
therapy required
group penetratin
and 80% g
cases of keratopla
SF6 sty. One

49
 group. case in
SF6
group
required
repeat
injection.
Jain et Retrosp Persisten Intracam Successf Pupillary Repeat
al., ective t DMD eral air ul block descemet
201434 case after (n=4) outcome glaucoma opexy
series primary Intracam in 92.3% in one gives
pneumati eral cases, case of good
c C3F8 No C3F8 visual
descemet (n=9) differenc and
opexy e in re- anatomic
(N-13) attachme al
nt rate outcome.
between
air and
C3F8.
EK
required
in 1 case
Garg Retrosp Post Intracam Complete Pupillary Shorter
et al., ective cataract eral re- block and interim
201624 case surgery C3F8 attachme raised period
series DMD nt in 72% IOP in and
(n=67) cases, 13.4% planar
Partial re- cases DMD has
attachme a higher
nt in rate of
18%, DM
100% reattach
success ment
rate in
planar
type
while
54% for
non-
planar
type.
1210
1211 Footnotes
1212 DMD- Descemet membrane detachment; VA- Visual acuity; DSAEK-
1213 Descemet stripping endothelial keratoplasty; CDVA- Corrected distance visual
1214 acuity; ASOCT- Anterior segment optical coherence tomography; C3F8-
1215 Perfluoropropane; IOP- Intra-ocular pressure; SF6- Sulphur hexafluoride; EK-
1216 Endothelial keratoplasty; DM- Descemet membrane.

50
 Table 1: Risk factors for DMD

Pre-operative Intra-operative Post-operative/

Delayed causes
Old age Clear corneal incision Factors for
(small, oblique, ragged) Spontaneous/
bilateral DMD
Dense cataract Blunt instrumentation Abnormality in DSI
Lack of adequate Inadvertent damage by Corneal ectatic
anaesthesia instruments disorders
Previous history of chemical Total ultrasound time > 60 Endothelial disorders
injury seconds like FECD
Corneal neovascularization

Footnotes: DMD- descemet membrane detcahment, FECD- Fuch’s endothelial

corneal dystrophy, DSI- Descemet Stromal Interface
 Table 2: Classifications of DMD

1. HELP algorithm for management of DMD38

Medical Management Surgical Management

Extent Height Length Extent Height Length
Zone 1 <100 µ <1mm Zone 1 100-300 µ 1-2 mm
>300 µ >2mm
Zone 2 <100 µ <1mm Zone 2 >300 µ >2mm
100-300 µ 1-2 mm
Zone 3 <100 µ <1 mm
100-300 µ 1-2 mm

>300 µ >2 mm

2. ASOCT based management algorithm for DMD65

Location of DMD Configuration Management

Superior half of Planar edges Intracameral air

cornea Scrolled edges Intracameral C3F8
Inferior half of cornea Planar edges Intracameral C3F8
Scrolled edges Intracameral C3F8
Extensive Intracameral C3F8
involvement of cornea

Footnotes: DMD- Descemet membrane detcahment, C3F8- Perfluoropropane,

HELP: Height extent length pupil based, ASOCT- Anterior segment optical
coherence tomography
 Table 3 : Management Outcomes in DMD

Author Study Type Sample size Intervention Outcome Complication Clinical

Implication
Odayappan Retrospective Post-cataract Air Successful re- Persistent DMD Air
et al., case series surgery DMD descemetopexy attachment (21.8%) descemetopexy
201855 n=112 after primary Corneal is safe and
descemetopexy decompensation effective for
71%. (7.3%) management of
15 patients Appositional DMD
underwent angle closure
repeat (18%)
descemetopexy Pupillary block
with 60% with air (2.7%)
success rate. Uveitis (2.7%)
VA >6/18 in
75% cases at 1
month
DSAEK- 7.3%
cases
Kumar et Prospective Post Phaco- Intervention Successful Pupillary block ASOCT based
al., 201538 case series emulsification based on HELP outcome in glaucoma (7.7%) algorithm is
DMD algorithm 95.8% cases of effective in
surgical management of
Surgical therapy therapy and cases post-
n=96 96.9% cases of surgical DMD
Medical therapy medical with severe
n=65 therapy. corneal oedema
No difference
in CDVA
Sharma et Prospective Post intra- ASOCT guided Success rate Two cases in C3F8 should be
al., 201565 case series ocular surgery management was 100%. C3F8 group had preferred for
DMD algorithm raised IOP. One inferior DMD
N-37 case required and superior
repeat injection DMD with
scrolled edge
Jain et al., Retrospective Post cataract Intracameral air Overall success Pupillary block Air is better
201333 study surgery DMD (n=24) rate was 95% glaucoma in than C3F8 with
N-60 Intracameral with no 11.7% cases less ocular
C3F8 (n=36) difference intracameral complications
between the C3F8 group
groups. VA was
better in the air
subgroup
Chaurasia Retrospective Post cataract Intracameral air Success rate Raised IOP in Air can be
et al., study surgery DMD was 92.8%. VA 14.3% cases safely used for
201210 N-14 was > 20/40 in pneumatic
11 cases descemetopexy
Marcon et Retrospective Post cataract Medical therapy Successful One case in each
al., 200250 case series surgery DMD (n=10) outcome in group had
N-15 Intracameral SF6 90% cases of treatment failure
(n=5) medical and required
therapy group penetrating
and 80% cases keratoplasty. One
of SF6 group. case in SF6 group
required repeat
injection.
Jain et al., Retrospective Persistent DMD Intracameral air Successful Pupillary block Repeat
201432 case series after primary (n=4) outcome in glaucoma in one descemetopexy
pneumatic Intracameral 92.3% cases, case of C3F8 gives good
descemetopexy C3F8 No difference visual and
(N-13) (n=9) in re- anatomical
attachment outcome.
rate between
air and C3F8.
EK required in
1 case
Garg et al., Retrospective Post cataract Intracameral Complete re- Pupillary block Shorter interim
201622 case series surgery DMD C3F8 attachment in and raised IOP in period and
 (n=67) 72% cases, 13.4% cases planar DMD has
Partial re- a higher rate of
attachment in DM
18%, reattachment
100% success
rate in planar
type while 54%
for non-planar
type.

Footnotes
DMD- Descemet membrane detachment; VA- Visual acuity; DSAEK- Descemet stripping endothelial keratoplasty; CDVA-
Corrected distance visual acuity; ASOCT- Anterior segment optical coherence tomography; C3F8- Perfluoropropane; IOP-
Intra-ocular pressure; SF6- Sulphur hexafluoride; EK- Endothelial keratoplasty; DM- Descemet membrane.