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Purpose: To study the influence of different intraoperative air tamponade times on graft adherence after Descemet membrane endothelial keratoplasty (DMEK)., Methods: In this interventional case series, we evaluated 117 eyes with Fuchs endothelial corneal dystrophy (FECD) that underwent DMEK using intraoperative air tamponade times of 60 minutes (group I; n = 39), 45 minutes (group II; n = 39), or 30 minutes (group III; n = 39). At 1 and 6 months postoperatively, graft adherence status, endothelial cell density, central pachymetry, and postoperative complications were recorded., Results: At 1 month, 19 of the 117 eyes (16.2%) showed a clinically significant detachment (>1/3 of the graft surface area and affecting visual axis): 6 eyes in group I (15.4%), 5 eyes in group II (12.8%), and 8 eyes in group III (20.5%) (P = 0.82). A minor detachment (<1/3 of the graft surface area and not affecting visual axis) was observed in 6 eyes in group I (15.4%), in 7 eyes in group II (17.9%), and in 4 eyes in group III (10.3%) (P = 0.82). The overall rebubbling rate was 11%, with no difference among the groups (P = 0.07). Mean endothelial cell density decrease at 6 months was 41% (±17%) (P = 0.56), whereas mean central pachymetry decreased by 23 (±10) % (P = 0.77), with no differences between the groups., Conclusions: The incidence of graft detachment after DMEK for FECD did not differ between the eyes that had a 60-, 45-, or 30-minute intraoperative air tamponade. Reducing the intraoperative air tamponade time to 30 minutes may be considered for DMEK in eyes with uncomplicated FECD.

Purpose: To evaluate early changes in visual function and visual quality parameters after Descemet membrane endothelial keratoplasty (DMEK) and to compare the outcomes with healthy controls., Methods: Thirteen patients who underwent DMEK and 14 controls were evaluated. All subjects underwent visual function evaluation, including visual acuity under photopic and mesopic lighting conditions and contrast sensitivity (CSV) tests CSV 1000 and Pelli-Robson. Corneal parameters were assessed with Oculus Pentacam. Corneal mean keratometry (Km), corneal densitometry values, and low and high order aberrations (LOA and HOA) were recorded. In DMEK patients, all tests were performed before surgery and 1 and 6 months after surgery., Results: In patients who underwent DMEK, photopic visual acuity improved from 0.59 to 0.31 at 1 month ( p =0.013) and 0.13 at 6 months ( p =0.008); mesopic visual acuity and all contrast sensitivity values (both CSV and Pelli-Robson test) improved significantly in the first month ( p < 0.005). A significant decrease was observed in corneal density in the 0-2 mm ring (from 43.83 to 35.60, p =0.043) and mean posterior Km (from -5.84 to -6.80, p =0.005) in the first month. Corneal HOAs and all corneal densities improved at 6 months after DMEK ( p < 0.05). All visual function parameters and corneal aberrations remained lower and higher, respectively, compared with healthy controls ( p < 0.05). Corneal densities were comparable with controls at 6 months after DMEK ( p > 0.05)., Conclusions: Patients undergoing DMEK present visual function improvement and a decrease in corneal density at 1 month after surgery. Decrease in corneal posterior HOAs can be observed at 6 months. However, visual function outcomes and corneal aberrations remained worse compared with healthy controls.

Purpose: To describe the clinical outcome and histopathology of Descemet membrane endothelial keratoplasty (DMEK) performed for secondary graft failure after penetrating keratoplasty (PK)., Methods: A total of 11 eyes from 10 patients who underwent DMEK for secondary PK graft failure at a tertiary referral center were included in this retrospective study. Best-corrected visual acuity, endothelial cell density, and central pachymetry were evaluated before and at regular time intervals up to 36 months after DMEK and complications were recorded; 1 post mortem cornea was available for light microscopy., Results: At their last follow-up visit (on average, 16 months after DMEK), 7 of 11 transplanted corneas were clear. In the 7 eyes with clear grafts, 5 had a best-corrected visual acuity of ≥20/25 (≥0.8), central pachymetry averaged 535 (±70) μm, and endothelial cell density averaged 1045 (±500) cells/mm. Of the 11 eyes, 4 required rebubbling in the early postoperative phase; 1 eye was left with a small (<1/3) detachment. Light microscopy of the pathology specimen showed complete attachment of the DMEK graft onto the preexisting PK posterior stroma, with interface scarring over DMEK graft folds and underneath the graft area that had initially been detached., Conclusions: DMEK may be a viable option to manage secondary PK graft failure with acceptable outcomes in many cases. Rebubbling for graft detachment may be anticipated, especially because of preexisting glaucoma conditions (severe decompensation, hypotony, and tubes from glaucoma-draining devices). Graft reattachment may occur through interface scarring.

Purpose: To assess the clinical outcome after successful rebubbling procedures for visually significant graft detachment after Descemet membrane endothelial keratoplasty (DMEK)., Methods: From a total of 760 consecutive DMEK surgeries, 41 eyes required rebubbling. Of those, 33 eyes of 31 patients were successful and were included in our retrospective outcome analysis study. Main outcome measures were compared with those of matched controls with uneventful primary DMEK (attached DMEK grafts without rebubbling). Rebubbling was performed on average 25 (±20) days (range 7-91 days) after DMEK. All eyes were evaluated for best-corrected visual acuity, endothelial cell density (ECD), pachymetry, and complications up to 6 months after rebubbling., Results: At 6 months after DMEK, best-corrected visual acuity in rebubbled eyes did not differ from that in control eyes (P = 0.514). The mean ECD decrease was higher in rebubbled than in control eyes (54% vs. 35%, respectively, P = 0.001). Pachymetry did not differ between both groups (P = 0.153). After rebubbling, one buphthalmic eye showed temporary intraocular pressure elevation and 5 eyes had minor graft edge detachment that did not require further treatment., Conclusions: Rebubbling for DMEK graft detachment may result in similar visual outcomes as in uncomplicated DMEK, when performed within the first 6 to 8 postoperative weeks. However, rebubbled eyes may have lower ECD, which may be attributed to additional air bubble trauma and/or selection bias through more extensive manipulation during initial DMEK or higher risk of graft detachment in more complicated eyes.

Purpose: To describe the 10-year clinical outcome of the first patient worldwide who underwent Descemet membrane endothelial keratoplasty (DMEK)., Methods: In 2006, a 63-year-old man presented at the Melles Cornea Clinic, Rotterdam, with bilateral Fuchs endothelial dystrophy and cataract. After phacoemulsification, in vivo DMEK was performed in the left eye and 10 months later in the right eye. Best spectacle-corrected visual acuity (BSCVA), endothelial cell density, pachymetry, and complications were recorded every 6 months over a 10-year period., Results: BSCVA in the left eye improved from 20/60 (0.3) before surgery to 20/17 (1.2) at 1 month, and remained stable over 10 years, ranging from 20/20 (1.0) to 20/13 (1.5). BSCVA in the right eye improved from 20/50 (0.4) preoperative and 20/60 (0.3) at 1 month to 20/25 (0.8) at 3 months and 20/17 (1.2) at 6 months, ranging from 20/25 (0.8) to 20/17 (1.2) over 9 years. Both eyes underwent YAG-laser-capsulotomy to manage posterior capsule opacification at 5 and 4 years after DMEK, respectively. Endothelial cell density in the right and left eyes, respectively, decreased by 43% and 45% at 1 year, 52% and 59% at 5 years, and 72% and 68% at 10/9 years, respectively. No intraoperative or postoperative complications occurred; at the last follow-up, both corneas were clear., Conclusions: The first DMEK patient worldwide may show all short and long-term characteristics of this endothelial keratoplasty technique: outstanding patient satisfaction, quick visual recovery, low incidence of complications, and graft longevity. Published studies in the past decade would suggest that this case was the start of a new era in corneal transplantation.

Background/aims: To evaluate the clinical outcome of a full-diameter, untrephined, semicircular Descemet graft in a consecutive series of Descemet membrane endothelial keratoplasty (hemi-DMEK), potentially allowing the harvesting of two grafts from a single donor corneoscleral rim., Methods: Interventional case series of 10 eyes of 10 patients with Fuchs endothelial dystrophy. Best corrected visual acuity (BCVA), endothelial cell density (ECD) and central corneal thickness (CCT) were evaluated up to 6 months postoperatively, and intraoperative and postoperative complications were recorded., Results: Hemi-DMEK was successful in 9 out of 10 eyes; one eye showed persistent graft detachment despite rebubbling and underwent a secondary DMEK. BCVA improved in all successful hemi-DMEK eyes: at 6 months 100% of eyes (n=7) reached ≥20/40 (≥0.5), 86% (n=6) ≥20/25 (≥0.8), 29% (n=2) ≥20/20 (≥1.0) and 14% (n=1) reached 20/17 (≥1.2). Two eyes were excluded from visual analysis due to low visual potential. Preoperative donor ECD declined from 2744 (±181) cells/mm 2 to 940 (±380) cells/mm 2 centrally at 6 months postoperatively (n=9), with (donor and/or host) endothelial cell redistribution over bare stromal areas adjacent to the graft. Average CCT decreased from 745 (±153) µm preoperatively to 520 (±37) µm at 6 months. Four eyes required rebubbling for visually significant graft detachment. No other complications occurred throughout the study period., Conclusions: Hemi-DMEK may give visual outcomes similar to those in conventional DMEK. If ECD decrease and graft detachment rate would prove acceptable in larger series, hemi-DMEK could have the potential to double the availability of donor tissue for endothelial keratoplasty., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose: To evaluate the midterm outcomes of Descemet membrane endothelial keratoplasty (DMEK) up to 4-7 years postoperatively., Design: Retrospective, consecutive interventional case series., Methods: A total of 250 consecutive eyes of 209 patients who underwent DMEK at our institute and had potentially at least 4 years of follow-up. Main outcome measures were best-corrected visual acuity (BCVA), endothelial cell density (ECD), central corneal thickness (CCT), graft survival rate, and postoperative complications., Results: At 6 months postoperatively, 73% of the eyes reached a BCVA of ≥20/25 (0.8) and 44% ≥20/20 (1.0), and remained stable up to 7 years (P = .7114). ECD dropped by 33.9% in the first 6 months, and then declined by a yearly rate of 9.0%. CCT did not show a significant change after 6 months up to 7 years (P = .8447). The cumulative graft survival rate at 4 and 7 years was 0.96 (95% confidence interval [0.93, 0.99]). Rebubbling procedures were performed in 4.4% of eyes, all within the first 6 postoperative months. Repeat transplantations were performed in 15.2% of cases to manage greater than one third graft detachment (11.6%), primary graft failure (1.6%), or secondary graft failure (2.0%), with the majority (79%) of repeat transplantations performed within the first year. After 6 months, the main complications were allograft rejection (2.4%) and secondary graft failure (2.0%)., Conclusions: The visual acuity level achieved at 6 months after DMEK may remain stable up to at least 4-7 years; ECD shows a constant, slow decrease; and complications after the first 6 months occur in <5% of cases., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the ability of Swept-source optical coherence tomography (SS-OCT) in detecting early endothelial graft detachment after Descemet membrane endothelial keratoplasty (DMEK) and to determine the possible causes of graft detachment using 2 different protocols for anterior segment (AS) imaging., Methods: Eight eyes from 8 consecutive DMEK surgeries were evaluated. High-resolution images were captured with SS-OCT using 2 different radial protocols for AS imaging (16- and 6-mm radial protocols). Central and peripheral corneal changes were evaluated., Results: All eyes developed early graft detachment detectable with the SS-OCT. The 16-mm radial protocol scanned the cornea detecting early graft detachment in 6 out of 8 cases. The 6-mm radial protocol provided detailed images of the cornea, detecting early detachment in all cases. Stromal irregularities and small remnants only detectable using SS-OCT were the possible cause of detachment in 3 cases. One of the 8 eyes had air reinjection. The detachment in that eye was apparent by slit-lamp examination. The detachments spontaneously resolved in the other 7 eyes. AS SS-OCT evaluation was found to have added diagnostic value to biomicroscopy in 5 of these eyes (64.5%)., Conclusions: AS SS-OCT is sensitive in detecting early graft detachment after DMEK. The 16-mm radial protocol of Triton SS-OCT is superior regarding quick scan of the entire cornea providing a general visualization of the DMEK graft. The 6-mm radial protocol provides detailed corneal imaging of a selected area, which is useful for evaluating structural alterations that are not detectable with larger scans and may affect the adherence of the endothelial graft.

Purpose: To describe the presence of "salt and pepper endothelium", that is, typical cellular inclusion bodies in a patient with Fuchs endothelial corneal dystrophy (FECD), that recurred in the donor corneal endothelial cells after Descemet membrane endothelial keratoplasty (DMEK)., Methods: A 76-year-old man underwent DMEK for FECD in his left eye. Routine specular microscopy imaging, best-corrected visual acuity measurements, and pachymetry measurements were performed before and after surgery., Results: Besides large guttae indicating FECD, preoperative specular microscopy images showed variable-sized dark cellular inclusion bodies in the endothelial cells. One month after DMEK, donor endothelial cells appeared normal; however, at 3 months, the typical inclusion bodies reappeared and progressed slowly within a 4-year follow-up period. Both best-corrected visual acuity and pachymetry were stable throughout the study period., Conclusions: "Salt and pepper endothelium" recurred after the host tissue was exchanged by donor Descemet membrane, that is, a DMEK graft. These changes may indicate that either the donor corneal endothelial cell morphology is modified by adjacent tissue structures or that it is completely replaced by recipient endothelium within the first months after surgery.

Purpose: To describe specific maneuvers and technical modifications to the standardized "no-touch" technique of Descemet membrane endothelial keratoplasty (DMEK) to successfully handle the presence of a glaucoma drainage device (GDD) tube in the anterior chamber of an eye with a failed primary penetrating keratoplasty (PK) graft., Methods: A 42-year-old male patient underwent DMEK because of a failed primary PK graft in his phakic right eye. The patient was then evaluated at 3 and at 6 months after surgery., Results: A modified no-touch DMEK technique proved a feasible treatment option for a decompensated primary PK graft in the presence of a long GDD tube., Conclusions: With specific technical modifications DMEK can be successfully performed in eyes with decompensated primary PK grafts in the presence of a long GDD tube. The very thin DMEK graft allows positioning between the GDD tube and the failed PK graft, leaving the tube in place.

Objective: To evaluate the clinical outcome of mid-stromal isolated Bowman layer transplantation, a new surgical technique to reduce and stabilize ectasia in eyes with advanced keratoconus, to postpone penetrating keratoplasty or deep anterior lamellar keratoplasty, and to enable continued daily contact lens wear., Design: Prospective, nonrandomized cohort study at a tertiary referral center., Participants: Twenty-two eyes of 19 patients with progressive, advanced keratoconus not eligible for ultraviolet cross-linking., Interventions: The mid-stroma was manually dissected and an isolated donor Bowman layer was positioned within the stromal pocket., Main Outcome Measures: Before and up to 36 months after surgery (mean follow-up, 21±7 months), best spectacle-corrected visual acuity (BSCVA), best contact lens-corrected visual acuity (BCLVA), Scheimpflug-based corneal tomography measurements, endothelial cell density, biomicroscopy, refraction, and intraoperative and postoperative complications were recorded., Results: Two surgeries were complicated by an intraoperative perforation of Descemet membrane; no other intraoperative or postoperative complications were observed. Maximum keratometry decreased on average from 77.2±6.2 diopters (D) to 69.2±3.7 D (P < 0.001) at 1 month after surgery and remained stable thereafter (P ≥ 0.072). Mean BSCVA improved from 1.27±0.44 logarithm of the minimum angle of resolution units before surgery to 0.90±0.30 logarithm of the minimum angle of resolution units 12 months after surgery (P < 0.001), whereas BCLVA remained stable (P = 0.105). Mean thinnest-point pachymetry increased from 332±59 μm before surgery to 360±50 μm at the latest follow-up (P = 0.012), and no change in endothelial cell density was found (P = 0.355)., Conclusions: With isolated Bowman layer transplantation, reduction and stabilization of corneal ectasia was achieved in eyes with progressive, advanced keratoconus. Given the low risk for complications, the procedure may be performed to postpone penetrating or deep anterior lamellar keratoplasty., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the clinical outcome of 500 consecutive cases after Descemet's membrane endothelial keratoplasty (DMEK) and the effect of technique standardization., Design: Prospective, interventional case series at a tertiary referral center., Participants: A total of 500 eyes of 393 patients who underwent DMEK for Fuchs' endothelial corneal dystrophy, bullous keratopathy, or previous corneal transplant failure., Methods: Best-corrected visual acuity (BCVA), endothelial cell density (ECD), pachymetry, and intraoperative and postoperative complications were evaluated before and 1, 3, and 6 months after DMEK., Main Outcome Measures: Comparison between 2 groups (group I: cases 1-250, outcome of "early surgeries" during transition to technique standardization; group II: cases 251-500, outcome of "late surgeries" after technique standardization)., Results: At 6 months, 75% of eyes reached a BCVA of ≥20/25 (≥0.8), 41% of eyes achieved ≥20/20 (≥1.0), and 13% of eyes achieved ≥20/18 (≥1.2) (n=418) when excluding eyes with ocular comorbidities (n=57). When including all available eyes at 6 months (n=475), 66% of eyes reached a BCVA of ≥20/25 (≥0.8), and 36% of eyes achieved ≥20/20 (≥1.0). Mean ECD decreased by 37% (±18%) to 1600 (±490) cells/mm2 (n=447) at 6 months (P<0.001). Postoperative pachymetry averaged 525 (±46) μm compared with 667 (±92) μm preoperatively (P<0.001). None of these parameters differed among the 2 groups (P>0.05). (Partial) graft detachment presented in 79 eyes (15.8%), and 26 eyes (5.2%) required a secondary surgery within the first 6 months (re-bubbling in 15, secondary keratoplasty in 11). With technique standardization, the postoperative complication rate decreased from 23.2% to 10% (P<0.001) and the rate of secondary surgeries decreased from 6.8% to 3.6% (P=0.10)., Conclusions: In comparison with earlier endothelial keratoplasty techniques, DMEK may consistently give higher visual outcomes and faster visual rehabilitation. When used for the extended spectrum of endothelial pathologies, DMEK proved feasible with a relatively low risk of complications. Technique standardization may have contributed to a lower graft detachment rate and a relatively low secondary intervention rate. As such, DMEK may become the first choice of treatment in corneal endothelial disease., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the clinical outcome and complications of repeat Descemet membrane endothelial keratoplasty (re-DMEK)., Design: Retrospective case series study at a tertiary referral center., Participants: From a series of 550 consecutive DMEK surgeries with ≥ 6 months follow-up, 17 eyes underwent re-DMEK for graft detachment after initial DMEK (n = 14) and/or endothelial graft failure (n = 3). The outcomes were compared with an age-matched control group of uncomplicated primary DMEK surgeries., Methods: The re-DMEK eyes were evaluated for best-corrected visual acuity (BCVA), densitometry, endothelial cell density (ECD), pachymetry, and intraoperative and postoperative complications., Main Outcome Measures: Feasibility and clinical outcome of re-DMEK., Results: In all eyes, re-DMEK was uneventful. At 12 months, 12 of 14 eyes (86%) achieved a BCVA of ≥ 20/40 (≥ 0.5); 8 of 14 eyes (57%) achieved ≥ 20/25 (≥ 0.8), 3 of 14 eyes (21%) achieved ≥ 20/20 (≥ 1.0), and 1 eye (7%) achieved 20/17 (1.2); 5 eyes were fitted with a contact lens. Average donor ECD decreased from 2580 ± 173 cells/mm(2) before to 1390 ± 466 cells/mm(2) at 6 months after surgery, and pachymetry from 703 ± 126 μm to 515 ± 39 μm, respectively. No difference in densitometry could be detected between re-DMEK and control eyes (P = 0.99). Complications after re-DMEK included primary graft failure (n = 1), secondary graft failure (n = 2), graft detachment requiring rebubbling (n = 1), secondary glaucoma (n = 2), cataract (n = 1), and corneal ulcer (n = 1). One eye received tertiary DMEK., Conclusions: In the management of persistent graft detachment and graft failure after primary DMEK, re-DMEK proved a feasible procedure. Acceptable BCVA may be achieved, albeit lower than after DMEK in virgin eyes, and some cases may benefit from contact lens fitting. Complications after re-DMEK may be better anticipated than after primary DMEK because graft detachment and graft failure tended to recur, suggesting that intrinsic properties of the host eye play a role in graft adherence and graft failure., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Importance: Surgeons starting to perform Descemet membrane endothelial keratoplasty (DMEK) should be informed about the learning curve and experience of others., Objective: To document the clinical outcome of standardized "no-touch" DMEK and its complications during the learning curves of experienced surgeons., Design, Setting, and Participants: Retrospective multicenter study. A total of 431 eyes from 401 patients with Fuchs endothelial dystrophy (68.2%) and bullous keratopathy (31.8%) underwent DMEK performed by 18 surgeons in 11 countries., Exposures: Descemet membrane endothelial keratoplasty., Main Outcomes and Measures: Best-corrected visual acuity (BCVA), endothelial cell density, and intraoperative and postoperative complications., Results: Of 275 eyes available for BCVA pooled analysis, BCVA improved in 258 eyes (93.8%), remained unchanged in 12 (4.4%), and deteriorated in 5 (1.8%). Two hundred seventeen eyes (78.9%) reached a BCVA of at least 20/40 (≥0.5), 117 (42.5%) at least 20/25 (≥0.8), and 61 (22.2%) at least 20/20 (≥1.0). Eyes with at least 6 months of follow-up (n = 176) reached similar BCVA outcomes. Mean (SD) decrease in endothelial cell density at 6 months was 47% (20%) (n = 133 [P = .02]). Intraoperative complications were rare, including difficulties in inserting, unfolding, or positioning of the graft (1.2%) and intraoperative hemorrhage (0.5%). The main postoperative complication was graft detachment (34.6%); 20.4% underwent a single rebubbling procedure, occasionally requiring a second (2.6%) and a third rebubbling (0.7%), and 17.6% underwent a second keratoplasty., Conclusions and Relevance: Our multicenter study showed that the standardized no-touch DMEK technique was feasible in most hands. The main challenges for surgeons starting to perform the procedure may be (1) to decide whether graft preparation is outsourced or performed during surgery, (2) to limit the number of graft detachments and secondary procedures, and (3) to obtain organ cultured donor corneal tissue.

Purpose: To evaluate corneal higher-order aberrations (HOAs) and backscattered light before and after Descemet membrane endothelial keratoplasty (DMEK) and their correlation with visual outcome., Design: Retrospective study., Methods: In a total of 118 consecutive eyes of 118 patients who underwent uneventful DMEK for Fuchs endothelial dystrophy at a tertiary referral center, best spectacle-corrected visual acuity (BSCVA), corneal HOAs, and backscattered light were evaluated preoperatively and at 6 months postoperatively. Outcome data were compared to an age-matched control group with uncomplicated eyes (n = 27)., Results: Compared to the control group, Fuchs endothelial dystrophy eyes, before as well as 6 months after DMEK, showed higher values of anterior and posterior HOAs and backscattered light (P < .033). Postoperative anterior HOAs and backscattered light (0-2 mm) were associated with lower 6-month BSCVA (positively related with logMAR BSCVA) (P ≤ .020). Anterior corneal HOAs did not change from preoperative to 6 months after DMEK (P = .649), while total posterior HOAs (RMS third to sixth Zernike order) and haze decreased (P < .001)., Conclusions: Anterior and posterior corneal HOAs, as well as backscattered light from the cornea, were elevated in eyes suffering from Fuchs endothelial dystrophy and remained higher throughout 6 months after DMEK. If present, anterior surface irregularities and anterior corneal haze may be the most important limiting factors in visual rehabilitation after DMEK., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the effect of subconjunctival anti-vascular endothelial growth factor (VEGF) ranibizumab on corneal and anterior segment neovascularization., Methods: In this experimental study and laboratory investigation, chemical cauterization was utilized to induce corneal neovascularization in 16 rabbits randomly divided in 2 equal groups. Cauterized eyes were either treated with 0.1 mL (1 mg) of subconjunctival ranibizumab or administered a sham injection. A third group of 4 rabbits served as control for side effects after ranibizumab administration. All animals were monitored daily for 14 days and the extent of corneal scarring and neovascularization was measured on days 1, 7, and 14. After enucleation, ocular tissues were separated under a surgical microscope and VEGF levels were measured with ELISA. Statistical analysis was performed to compare the extent of corneal neovascularization and VEGF levels between treated and untreated eyes., Results: Subconjunctival ranibizumab inhibited corneal neovascularization significantly both in the first and the second week compared to untreated controls (p = 0.006 and p = 0.001, respectively). The VEGF levels were significantly lower in all anterior segment tissues like the cornea, iris, aqueous humor, and conjunctiva of the treated eyes (p<0.01). The reduction of VEGF levels ranged from 19% to 73% in different ocular tissues. Corneal scarring was not significantly affected by anti-VEGF treatment (p = 0.7). No side effects were noticed., Conclusions: Early subconjunctival administration of ranibizumab may successfully inhibit alkali-induced corneal neovascularization in an animal model. Subconjunctival ranibizumab reduces VEGF levels significantly not only in the cornea and the bulbar conjunctiva but also in the aqueous humor and the iris.

Purpose: To describe how to approach eyes with phakic or pseudophakic bullous keratopathy that have an anterior chamber intraocular lens (AC IOL) using thin Descemet-stripping endothelial keratoplasty (thin-DSEK) or Descemet membrane endothelial keratoplasty (DMEK) with or without AC IOL removal., Setting: Tertiary referral center., Design: Comparative case series., Methods: Descemet membrane endothelial keratoplasty or thin-DSEK was performed in pseudophakic eyes with iris-claw AC IOLs (Group 1) or in phakic eyes with angle-supported AC IOLs (Group 2). In both groups, DMEK was routinely performed except in eyes with insufficient corneal transparency or a high risk for graft detachment. Preoperative surgical considerations, postoperative corrected distance visual acuity (CDVA), endothelial cell density, and complications were documented., Results: In Group 1, all AC IOLs were left in situ. In Group 2, AC IOLs were removed in 90% of cases. At 6 months, the CDVA was 20/40 (≥0.5 decimal) or better in 36% of eyes in Group 1 and 90% in Group 2. Graft detachment occurred in 20% of eyes and de novo or glaucoma exacerbation in 29%., Conclusions: Bullous keratopathy treatment in eyes with an AC IOL was feasible with DMEK. Intraocular lens removal may be required if postoperative complications are anticipated, but not to facilitate surgery. Overall, the surgical approach may aim to minimize postoperative complications; that is, thin-DSEK in eyes with low visual potential and/or concomitant pathology and DMEK in eyes with a phakic AC IOL and normal visual potential., (Copyright © 2013 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the incidence and causes of anterior corneal surface irregularities after successful Descemet membrane endothelial keratoplasty (DMEK) and the efficacy of contact lens fitting in these cases., Setting: Tertiary referral center., Design: Retrospective study of prospectively collected data., Methods: Eyes with a subnormal visual outcome or monocular diplopia after successful DMEK were fitted with a contact lens. These cases were evaluated with Pentacam rotating Scheimpflug camera imaging preoperatively and 6 months postoperatively, and outcomes were compared with those in a randomly selected DMEK control group., Results: In a series of 262 surgeries, 23 eyes (21 patients) were fitted with contact lenses; the control group comprised 23 eyes. Indications for contact lens fitting included (1) obvious corneal surface irregularities due to preexisting corneal scarring, (2) surface irregularities associated with longstanding preoperative stromal edema, and (3) undetectable optical imperfections. The postoperative corrected distance visual acuity (CDVA) with spectacles improved after contact lens correction (P<.001). Preoperative and postoperative irregularity indices were significantly higher in the contact lens group than in the DMEK control group (P<.05). Positive correlations were found between the duration of preoperative stromal edema and postoperative Scheimpflug camera indices (P<.02)., Conclusions: After successful DMEK, 23 of 262 eyes (9%) showed subnormal spectacle CDVA and/or monocular diplopia due to corneal scarring, surface irregularities, or undetectable optical imperfections that could be managed by contact lens fitting. Prolonged preoperative corneal edema for more than 12 months may be a risk factor for diffuse irregular astigmatism after DMEK., Financial Disclosure: Dr. Melles is a consultant to DORC International BV/Dutch Ophthalmic USA. No author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2013 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To identify causes of reduced visual acuity after Descemet stripping (automated) endothelial keratoplasty (DSEK/DSAEK) and to determine whether such eyes can be successfully 'repaired' with a secondary Descemet membrane endothelial keratoplasty (DMEK)., Methods: Twelve eyes of 12 patients, who underwent secondary DMEK to manage poor visual outcome after initial DSEK/DSAEK, were evaluated with biomicroscopy, Pentacam imaging, and specular and confocal microscopy, before and at 1, 3 and 6 months after DMEK., Results: Four causes of reduced optical quality of the transplanted host cornea could be identified in DSEK/DSAEK: five eyes (42%) showed large host-Descemet remnants within the visual axis during surgery; six eyes (50%) irregular graft thickness; six eyes subtle 'stromal waves'; and nine eyes (75%) high reflectivity at the donor-to-host interface. After DMEK graft replacement, all corneas cleared and achieved a best corrected visual acuity of ≥20/25 (≥0.8), except for one with a partial Descemet graft detachment. Pachymetry values decreased from 670 (±112) μm before to 517 (±57) μm after secondary DMEK. Higher-order aberrations (Coma and Trefoil) at the posterior surface tended to be lower (p = 0.07) in DMEK grafts than in DSEK/DSAEK grafts., Conclusion: Host-Descemet remnants at the donor-to-host interface, interface reflectivity, graft thickness irregularity and donor stromal contraction may contribute to poor visual outcome after DSEK/DSAEK, without causing permanent host corneal damage, as in most cases, complete visual recovery could be achieved by performing a secondary DMEK., (© 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To study the validity of endothelial polymegethism, pleomorphism, and "poor swelling" as tissue discard parameters in the immediate postmortem evaluation of human donor corneal endothelium., Methods: We retrospectively evaluated the quality of the endothelium at first and second evaluations for all processed corneas exhibiting moderate polymegethism, pleomorphism, or "poor swelling" in our eye bank over a 5-year period., Results: Out of 2008 eyes qualifying for our study, 422 corneas (21%) showed polymegethism, pleomorphism, or poor swelling at the first tissue evaluation immediately after excision of the corneoscleral button. In 363 (86%) of these corneas, a normal endothelial mosaic was observed at the second tissue evaluation after 7 to 21 days of organ culture, whereas only 59 (14%) still showed persistent polymegethism, pleomorphism, or "poor swelling" at that time point., Conclusions: A recovery of normal endothelial cell mosaic and "normal swelling" at the second evaluation suggests that cellular contour parameters do not relate to tissue viability, but rather to a cellular stress reaction. If so, the validity of endothelial cellular contour morphology as an early parameter in assessing the suitability of a donor cornea for transplantation may be reconsidered.

Purpose: To evaluate the predictive value of early anterior segment optical coherence tomography (AS-OCT) on graft adherence or detachment after Descemet's membrane endothelial keratoplasty (DMEK)., Design: Retrospective study of prospectively collected data at a tertiary referral center., Participants: A total of 87 eyes of 87 patients of a consecutive series of 142 DMEK surgeries., Methods: Anterior segment OCT was performed within the first hour after DMEK and at 1 week, 1 month, 3 months, and 6 months, and for each time interval detachments were classified as "none," ≤ 1/3 detachment, >1/3 detachment of the total graft surface area, or "complete" detachment. Throughout the study, no rebubbling procedures were performed., Main Outcome Measures: Graft adherence at various postoperative time intervals., Results: One-hour AS-OCT scans were more accurate at predicting the final 6-month graft adherence status than those at 1 week or 1 month. Grafts showing complete attachment or <1/3 detachment at 1 hour remained stable or improved in 73% of the cases at 1 week, 82% at 1 month, 86% at 3 months, and 90% at 6 months. All grafts attached at 1 week remained attached at 6 months. Graft detachments of >1/3 at 1 hour showed reattachment at 6 months in 25% of the cases, whereas 67.5% of the cases showed a persistent detachment of >1/3 at 6 months and 12.5% showed a complete detachment., Conclusions: The 1-hour AS-OCT scan showed the best predictive value on 6-month graft adherence status. The combined information of the 1-hour and 1-week AS-OCT scans may facilitate decision making about surgical reintervention after DMEK., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To define various Descemet graft unfolding techniques in Descemet membrane endothelial keratoplasty., Methods: In a retrospective analysis, the surgical videos of 100 consecutive Descemet membrane endothelial keratoplasty cases with at least 6 months of follow-up were evaluated and categorized. The Descemet graft unfolding methods were categorized into 4 basic techniques and 3 auxiliary techniques., Results: All Descemet membrane endothelial keratoplasty surgical procedures could be completed using (a combination of) 4 Descemet graft unfolding techniques: (1) standardized no-touch graft unfolding using a double roll, (2) carpet unrolling while fixating 1 graft edge (Dirisamer technique), (3) small air bubble-assisted unrolling (Dapena maneuver), (4) the single sliding cannula maneuver. Additional maneuvers included turning over the graft when oriented upside down (flushing); manual graft centration with a cannula; and bubble bumping to unfold peripheral inward folds. In 73% of surgical procedures, technique 1 was used, while a combination of techniques was used in 44% and auxiliary techniques in 62%. None of the techniques showed a correlation with the best-corrected visual acuity, endothelial cell density, or postoperative complication rate (P > .10)., Conclusions: Descemet membrane endothelial keratoplasty may be further facilitated by using controlled techniques for unfolding the Descemet graft inside the recipient anterior chamber, either as stand-alone techniques or used in various combinations.

Purpose: To investigate by optical coherence tomography (OCT) the evolution of the photoreceptor layer and its association with best-corrected visual acuity (BCVA) in optic disc pit (ODP) maculopathy after successful surgical treatment., Methods: Fourteen eyes of 14 patients were included in this study, and followed up from 36 to 95 months (mean 57.36 ± 18.32 months). The follow-up period started at the time of complete subretinal fluid absorption. Examination was performed by time-domain OCT before and after treatment. Spectral-domain OCT was used after treatment. Parameters assessed were type of elevation, central foveal thickness, time elapsed from onset to treatment, type of treatment, BCVA, and inner segment outer segment (IS/OS) junction line. The IS/OS junction was characterized after treatment as intact, interrupted, or absent (not distinguishable)., Results: Significant restoration of the IS/OS junction line was first noticed between 6 and 12 months after fluid absorption (p = 0.02; Wilcoxon signed rank test). Restoration was continuous up to the 24th month of postoperative examination after fluid absorption (p = 0.14; Wilcoxon signed rank test). BCVA was 0.99 ± 0.38 logMar before treatment, 0.81 ± 0.26 logMar (p = 0.011; paired t-test) immediately after fluid absorption and 0.61 ± 0.33 logMar (p = 0.026; one-way ANOVA) 24 months after fluid resolution. BCVA was significantly positively correlated with the integrity of the IS/OS junction line during follow-up (Pearson r = 0.775; p < 0.001)., Conclusions: The IS/OS junction restoration cannot be detected immediately after fluid resolution in the majority of cases. It became evident 6-12 months later and was completed 24 months after fluid absorption. Improvement in BCVA was noticed only during the first 2 years of follow-up. No significant changes were noticed in BCVA or the IS/OS line after 2 years. Among the studied variables, the final photoreceptor layer condition and BCVA immediately after fluid absorption are the main factors predicting final BCVA after successful surgical treatment of ODP maculopathy.

Purpose: To study the prognostic factors that influence best-corrected visual acuity (BCVA) outcome in patients with secondary epiretinal membrane (ERM) after retinal detachment surgery., Design: Retrospective case series., Methods: Forty-two patients with ERM were divided into macula-on and macula-off groups based on the macular status before retinal detachment surgery and were studied using the same spectral-domain optical coherence tomography device. Several variables, including the integrity of the external limiting membrane (ELM), the status of the photoreceptor inner segment/outer segment (IS/OS) junction line, and central foveal thickness were evaluated in 17 treated and 25 untreated patients. Linear regression analysis was used to determine the best combination of all variables affecting BCVA., Results: Final BCVA was significantly better in macula-on and macula-off eyes with intact ELMs and IS/OS junction lines (0.35 ± 0.18 logarithm of the minimal angle of resolution [logMAR] and 0.51 ± 0.17 logMAR, respectively) than in macula-off eyes with disrupted or absent ELMs and IS/OS junction lines (0.83 ± 0.17 logMAR and 1.04 ± 0.05 logMAR, respectively; P < .001, analysis of variance). Final BCVA also was better in the treated group than in the controls (0.55 ± 0.31 logMAR and 0.73 ± 0.26 logMAR, respectively; P = .05, t test). ELM and IS/OS junction line integrity were the main variables significantly affecting the final BCVA outcome (β = 0.42; P = .006, linear regression analysis). Disruption of the ELM and IS/OS junction line was observed in 21 of the 42 cases studied., Conclusions: ERM secondary to retinal detachment surgery is accompanied by a high incidence (50%) of IS/OS junction line and ELM disruption. Among the variables studied, the condition of the IS/OS junction layer and the ELM are the main factors that predict final BCVA after ERM peeling., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: Fibrous dysplasia is a primary orbital bone tumor, described as a benign disorder in which proliferation of fibrous tissue and osteoid replaces and distorts the bone from which it derives. Unilateral keratoconus is a rare entity. Herein, we report a case of an extensive ethmoidal fibrous dysplasia associated with ipsilateral keratoconus, and review the literature on the subject., Materials and Methods: A 22-year-old man presented with left painless proptosis evolving over 10 years. There was associated ipsilateral epiphora and gradual visual loss. On examination his visual acuity was 20/20 OD and CF OS. His left globe was displaced lateraly 12 mm, with 9 mm of proptosis. The extraocular movements were normal. Left nasolacrimal duct obstruction was noted. Clinical signs of keratoconus were present only in the left cornea. High resolution corneal topography confirmed unilateral keratoconus and a CT scan showed an ovoid mass with a well defined sclerotic margin arising from the left ethmoid sinus and invading the orbit., Results: The patient underwent resection of the lesion via a modified Lynch incision. Complete regression of proptosis was observed immediately after surgery. Histopathological examination revealed irregular trabeculae of woven bone in different levels of maturation in a moderately cellular fibrous matrix without nuclear atypia. Trabeculae were without osteoblastic rimming or osteoclastic resorption. There has been no recurrence over a 2-year follow-up period., Conclusion: To our knowledge, the coexistence of unilateral isolated craniofacial fibrous dysplasia with ipsilateral keratoconus has not been reported so far.

Purpose: To present our preliminary experience on intravitreal administration of an anti-tumor necrosis factor (TNF) monoclonal antibody for neovascular age-related macular degeneration (AMD)., Design: Prospective, noncomparative series of 3 patients previously treated with an anti-vascular endothelial growth factor agent., Methods: Two intravitreal injections of 0.05 ml containing infliximab were administered in the first (1 and 2 mg, 2 months apart), second (2 mg each, 2 months apart), and third patient (2 mg each, 3 months apart). Best-corrected visual acuity (BCVA) and central foveal thickness (CFT) were monthly assessed for up to 7 months., Results: In the first patient, BCVA increased from 20/200 to 20/100 and CFT decreased from 462 to 386 microm, 2 months after the first injection. The condition was further improved after the second injection (BCVA, 20/40; CFT, 210 microm), but recurrence occurred 7 months post-baseline. In the second patient, BCVA increased from 20/200 to 20/70 and CFT decreased from 512 to 420 and 184 microm, 2 and 4 months post-baseline, respectively. In the third patient, clinical improvement was documented after the first injection. A second injection attributable to recurrence resulted in improvement of BCVA from 20/100 to 20/30 and decrease of CFT from 388 to 282 microm, 2 months after the second injection., Conclusions: These findings, although insufficient to consider "off-label" treatment with intravitreal infliximab, provide in vivo evidence of a pathogenetic link of locally produced and/or acting TNF to neovascular AMD. A randomized study of consecutive intravitreal injections of infliximab for AMD may be warranted.

Background: Tumor necrosis factor (TNF) is known to play an important role in various immune-mediated ocular diseases; intravenous administration of the anti-TNF monoclonal antibody infliximab has proved beneficial in such cases. Since intravitreal injection (when available) is a substitute for systemic administration of various drugs targeting the eye, we aimed to evaluate the safety of intravitreal injection of infliximab in the rabbit eye., Methods: Seven groups of New Zealand white rabbits (four animals in each group) received a single unilateral intravitreal injection (0.1 ml) of increasing doses of infliximab (namely 1, 2, 5, 8, 10 or 20 mg infliximab [Remicade]) or a sham injection respectively. Slit-lamp biomicroscopy, fundoscopy and electrophysiology recordings, i.e. scotopic, photopic and flicker responses, were performed at baseline and after 1, 5, 10, 15, 30 and 45 days. Infliximab-injected eyes were compared with sham-injected and with uninjected fellow eyes (n = 28). Animals were euthanized on day 45 for histopathological examination of the retinas., Results: Clinical examination and electrophysiological testing were consistently unremarkable after either sham or 1 mg or 2 mg infliximab injections. In contrast, electrophysiological recordings were significantly reduced in a dose-dependent manner from day 1 through day 45, after 5, 8, 10 and 20 mg infliximab injections. Flicker responses were the most sensitive in detecting the lower toxic dose of 5 mg. Histopathological findings were similar in uninjected and sham-injected eyes, as well as after 1 mg or 2 mg infliximab injections. Consistent with the functional abnormalities, retinal deformities and diffuse edema were observed after injection of 5 mg or higher doses of infliximab., Conclusions: Intravitreal infliximab may be safely administered up to a dose of 2 mg in the rabbit eye. Such doses can be used in the design of future clinical trials assessing the effects of infliximab for selected patients with immune-mediated ocular conditions.

We report a patient with lattice corneal dystrophy type II, also known as Meretoja syndrome or familial amyloidosis Finnish type, who developed a corneal melt 15 days after uneventful phacoemulsification. Despite conservative treatment, the corneal melt resulted in perforation. Uneventful penetrating keratoplasty was performed, but delayed graft epithelial healing was noticed postoperatively. Corneal button histopathological evaluation confirmed the initial clinical diagnosis. To our knowledge, this is the first reported case of corneal melt and perforation in a patient with lattice corneal dystrophy type II.

Aim: Our purpose was to evaluate the possible effect of intravitreal ranibizumab on the fellow untreated eye with choroidal neovascularization (CNV) and subfoveal scarring associated with age-related macular degeneration (AMD)., Methods: A retrospective observational study was conducted. One hundred eighty-seven ranibizumab-treated patients diagnosed as having subfoveal CNV scarring in the untreated eye were compared with a control group of untreated unilateral subfoveal CNV scarring. Inclusion criteria concerning treated eyes in the ranibizumab group complied with the MARINA and ANCHOR studies. Demographic data, clinical course, visual acuity, fluorescein angiography and optical coherence tomography findings were evaluated., Results: Clinical improvement was confirmed in 24% of the patients in the ranibizumab group and in only 12.9% of the controls. Improvement was noted as early as 2-4 months (2.83 + or - 0.75 months) after the initiation of treatment in the fellow eye compared with 33.25 + or - 9.43 months in the control group (p = 0.01; Mann-Whitney U test). Kaplan-Meier curves demonstrate the positive impact of ranibizumab on the visual acuity of the fellow untreated eye (p = 0.016; Log-Rank test)., Conclusions: Ranibizumab might induce some therapeutic effect in selected cases of end-stage CNV scarring, which needs to be further examined. The VEGF levels in the compartments of the fellow eye of patients with age-related macular degeneration treated with ranibizumab need to be further evaluated., (Copyright 2009 S. Karger AG, Basel.)

Purpose: To evaluate the effect of subconjunctival injection of bevacizumab on experimentally induced corneal neovascularization., Design: Experimental animal study., Methods: Twelve New Zealand white rabbits were involved, divided equally into four groups. Only one eye per rabbit was used. Topical instillation of 10 microl 5% NaOH solution was used, under general anesthesia, to induce corneal neovascularization secondary to corneal alkali burn in groups 2, 3, and 4. A single dose of 3.75 mg (25 mg/ml) bevacizumab was injected subconjunctivally. Group 1 (control group 1) was neither cauterized nor treated. Group 2 (control group 2) received a sham injection of balanced salt solution on day 14. Group 3 was treated on day 14 (after corneal neovascularization had been established). Group 4 was treated on day 1. Digital photographs were obtained and analyzed during the entire 28-day procedure. The area of neovascularization and scarring were measured in terms of the percentage of corneal surface affected., Results: On day 28, the difference of neovascularization between groups 2, 3, and 4 was found to be statistically significant at the .05 level (one-way analysis of variance [ANOVA]): group 4 (4.7%+/-3.1%).1, one-way ANOVA). No side effects were noted., Conclusions: Subconjunctival administration of bevacizumab inhibits corneal neovascularization effectively in the rabbit experimental model, especially if administered early.