Decellularized Descemet Membrane Anterior Keratoplasty With Allogeneic Simple Limbal Epithelial Transplantation for Partial Limbal Stem Cell Deficiency Following Partial Keratolimbal Allograft Failure.

PURPOSE: The purpose of this study was to describe the use of Descemet membrane anterior keratoplasty (DMAK) with modified allogeneic simple limbal epithelial transplantation to treat a case of partial limbal stem cell deficiency (LSCD) following keratolimbal allograft failure. METHODS: Case report. RESULTS: A 21-year-old woman with autoimmune polyglandular syndrome-related LSCD presented with pain and decreased vision. There was partial failure and recurrence of LSCD after a severe/acute keratolimbal allograft rejection that led to persistent epithelial defects refractory to conservative therapy. This was treated with a superficial keratectomy and placement of a DMAK. A modified allogeneic simple limbal epithelial transplantation was performed with an overlying amniotic membrane and temporary tarsorrhaphy. There was epithelialization of the corneal surface by 3 to 4 weeks with an improved ocular surface. Despite partial recurrence of late staining, the cornea has remained epithelized, vision has improved, and the patient has remained pain-free more than 1.5 years following the procedure. CONCLUSIONS: DMAK may be a long-term substrate to help improve and maintain epithelization of the cornea up to 1.5 years. DMAK may be a viable alternative to using amniotic membrane as a scaffold in allogeneic simple limbal epithelial transplantation for treatment of partial LSCD. While late epithelial staining recurred in our patient, DMAK appears to prevent recurrent epithelial defects and reduce ocular surface pain, conveying an improvement in quality of life in patients at high risk of rejection/failure.

Topical Tacrolimus Compared With Oral Tacrolimus for Postoperative Immunosuppression in Primary Keratolimbal Allograft.

PURPOSE: The aim of this study was to compare outcomes between topical tacrolimus and oral tacrolimus as the primary calcineurin inhibitor for postoperative immunosuppression after primary keratolimbal allograft (KLAL) transplantation for limbal stem cell deficiency (LSCD). METHODS: We performed a retrospective, comparative cohort study at a single tertiary referral center (University of MN) of all patients who underwent primary KLAL between 2014 and 2021. Eyes were grouped into those which received topical tacrolimus as the only calcineurin inhibitor (topical group) and eyes in which patients received oral tacrolimus with or without topical tacrolimus (oral group). Clinical and donor tissue data were obtained and compared between the 2 groups. RESULTS: In total, 27 eyes of 22 patients (median age 42 years, range 20-79 years) were included, of which 18 eyes were in the oral group and 9 eyes were in the topical group. The mean follow-up time was 33.2 ± 22.6 months. The most frequent etiology of LSCD was alkaline burn (33.3%). At 36 months, graft failure occurred in 6 eyes in the oral group (33.3%) and 2 eyes in the topical group (22.1%) ( P = 0.57). The failure rate in the oral group was 9.1 per 1000 person-months versus 8.4 per 1000 person-months in the topical group ( P = 0.96). The median improvement in BCVA was logMAR -0.975 and logMAR -0.45 for the oral and topical group, respectively ( P = 0.50). CONCLUSIONS: With careful patient selection, topical tacrolimus may be a viable alternative to oral tacrolimus in KLAL.

Clinical applications of bioengineered tissue-cellular products for management of corneal diseases.

PURPOSE OF REVIEW: To discuss bioengineered tissue-cellular products for treatment of corneal diseases that are currently in clinical use. These include tissue-cellular products that have received regulatory approval, are being used off-label in clinical practice, or are in active use in clinical trials. RECENT FINDINGS: Due to the global shortage of donor corneal tissue, significant efforts have been made to develop bioengineering tissue-cellular products that can replace or augment the use of cadaveric tissue for corneal transplantation. The development of carrier substrates to support transplantation of cultivated limbal epithelial transplantation (CLET) has been a growing area of research. CLET offers a promising therapeutic alternative to conventional simple limbal epithelial transplantation and keratolimbal allografts for treatment of limbal stem cell deficiency. Engineered tissue matrices and porcine-derived corneas are potential alternatives to human donor tissue in anterior lamellar keratoplasty for corneal ulcers and scars, as well as intrastromal transplants for advanced keratoconus. For endothelial disease, substrate supported cultured endothelial cell grafts, and synthetic barrier devices are promising alternative to traditional endothelial keratoplasties. SUMMARY: There has been increasing interest in cellular and acellular bioengineered tissue-cellular and synthetic products for treatment of corneal diseases, and many of these products have already seen clinical use. Industry and academia have important roles in advancing these products to later phase clinical trials and comparing them to conventional allograft approaches. Future development of full thickness donor corneas with cultivated epithelium, endothelium, and stromal keratocytes in a biosynthetic matrix will likely be an important next step in tissue alternatives. Continued progress in this field will be critical for addressing the global disease burden from corneal blindness.

Staged limbal stem cell transplantation and keratoplasty surgeries as a treatment for gelatinous drop-like corneal dystrophy.

Gelatinous drop-like corneal dystrophy (GDLD) is a rare autosomal recessive corneal dystrophy that has been associated with mutations in the TACSTD2 (M1S1) gene, which is normally expressed in corneal epithelial cells. GDLD is characterized by progressive deposition of amyloid in the corneal stroma with rapid recurrence in grafts after penetrating keratoplasty. We report of case of a patient with GDLD treated bilaterally with staged limbal stem cell transplantation and penetrating keratoplasty that resulted in long-term control of his disease. This case demonstrates that staged allogenic limbal stem cell transplantation, before or after penetrating keratoplasty, can be used to restore vision long-term in GDLD patients.

In vitro infection of human ocular tissues by SARS-CoV-2 lineage A isolates.

BACKGROUND: The purpose of this study was: [1] to evaluate the infectivity of two SARS-CoV-2 lineage A variants on human ocular tissues in vitro, and [2] to evaluate the stability of SARS-CoV-2 lineage A variants in corneal preservation medium. METHODS: Primary cultures of donor corneal, conjunctival, and limbal epithelium were inoculated with two lineage A, GISAID clade S isolates of SARS-CoV-2 (Hong Kong/VM20001061/2020, USA-WA1/2020), to evaluate the susceptibility of the ocular tissue to infection. Flat-mounted Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK) grafts were inoculated with SARS-CoV-2 to evaluate the susceptibility of the endothelium to infection. All inoculated samples were immunostained for SARS-CoV-2 nucleocapsid (N)-protein expression to confirm positive infection. SARS-CoV-2 Hong Kong was then inoculated into cornea preservation media (Life4°C, Numedis, Inc.). Inoculated media was stored at 4oC for 14 days and assayed over time for changes in infectious viral titers. RESULTS: Corneal, conjunctival, and limbal epithelial cells all demonstrated susceptibility to infection by SARS-CoV-2 lineage A variants. Conjunctiva demonstrated the highest infection rate (78% of samples infected [14/18]); however, infection rates did not differ statistically between cell types and viral isolates. After inoculation, 40% (4/10) of DSAEK grafts had active infection in the endothelium. SARS-CoV-2 lineage A demonstrated < 1 log decline in viral titers out to 14 days in corneal preservation media. CONCLUSIONS: SARS-CoV-2 lineage A variants can infect corneal, limbal, and conjunctival epithelium, as well as corneal endothelium. There was no statistical difference in infectivity between different lineage A variants. SARS-CoV-2 lineage A can survive and remain infectious in corneal preservation media out to 14 days in cold storage.

Management of Suprachoroidal Hemorrhage in a Patient With Boston Type I Keratoprosthesis.

Purpose: Suprachoroidal hemorrhage (SCH) is a rare but vision-threatening complication in patients with keratoprosthesis devices (KPro), particularly in the setting of concurrent glaucoma tube shunts. Although there are many approaches to draining an SCH, surgery can be especially challenging in these patients because a crowded anterior chamber, and frequent anterior extension of the SCH. Methods: A case report is discussed. Results: We describe a novel approach to surgical drainage of SCH in a 64-year-old monocular patient with a Type I Boston KPro, an Ahmed valve, and aphakia. Conclusion: Successful repair of appositional SCH in the context of KPro can be safely and effectively achieved by injecting viscoelastic through the backplate holes of the KPro, thereby providing internal tamponade within the vitreous compartment while liquefied hemorrhage is drained by sclerotomy.

Corneal perforation in ocular graft-versus-host disease.

PURPOSE: Corneal perforation is a rare, vision-threatening complication of ocular graft-versus-host disease (GVHD) and is not well understood. Our objective was to examine the clinical disease course and histopathologic correlation in patients who progressed to this outcome. METHODS: This study is a retrospective case series from four academic centers in the United States. All patients received a hematopoietic stem cell transplant (HSCT) prior to developing ocular GVHD. Variables of interest included patient demographics, time interval between HSCT and ocular events, visual acuity throughout clinical course, corticosteroid and infection prophylaxis regimens at time of corneal perforation, medical/surgical interventions, and histopathology. RESULTS: Fourteen eyes from 14 patients were analyzed. Most patients were male (86%) and Caucasian (86%), and average age at time of hematopoietic stem cell transplant was 47 years. The mean interval between hematopoietic stem cell transplant and diagnosis of ocular graft-versus-host disease was 9.5 months, and between hematopoietic stem cell transplant and corneal perforation was 37 months. Initial best-corrected visual acuity was 20/40 or better in 9 eyes, and all eyes had moderate or poor visual outcomes despite aggressive management, including corneal gluing in all patients followed by keratoplasty in 8 patients. The mean follow-up after perforation was 34 months (range 2-140 months). Oral prednisone was used prior to perforation in 11 patients (79%). On histopathology, representative specimens in the acute phase demonstrated ulcerative keratitis with perforation but minimal inflammatory cells and no microorganisms, consistent with sterile corneal "melt" in the setting of immunosuppression; and in the healed phase, filling in of the perforation site with fibrous scar. CONCLUSIONS: In these patients, an extended time interval was identified between the diagnosis of ocular graft-versus-host disease and corneal perforation. This represents a critical window to potentially prevent this devastating outcome. Further study is required to identify those patients at greatest risk as well as to optimize prevention strategies.

Acute anterior uveitis after topical interferon for conjunctival intraepithelial neoplasia (CIN).

Objective: Ocular surface squamous neoplasia (OSSN) is the most common type of non-melanocytic ocular surface tumor. Conjunctival intraepithelial neoplasia (CIN) is a type of OSSN that be medically managed by either topical interferon alpha-2b (IFN α-2b), 5-fluorouracil (5-FU), or mitomycin C. While a paradoxical response to IFN α-2b in the HIV population has been reported, we report a case of a paradoxical response in an immunocompetent individual. Methods: A 65-year-old immunocompetent female presents to the clinic with CIN. Results: She is started on topical IFN α-2b, resulting in an unexpected hypopyon, increased corneal epithelial defect, and increased size of the lesion. Switching to topical 5-FU resulted in decreasing size of the CIN lesion and resolution of the epithelial defect. Conclusions: Topical IFN α-2b can produce a paradoxical worsening of CIN lesions in some patients. Providers should be aware of this reaction, as well as the presenting signs and symptoms, to make appropriate treatment changes when treating CIN.

Trypan-Assisted Automated Endothelial Cell Loss Measurements Compared With Specular Microscopy.

PURPOSE: The aims of this study were 1) to compare area of cell loss (ACL) on trypan staining with ACL on specular imaging and 2) to evaluate the use of automated software for measuring ACL on trypan staining. METHODS: Donor corneas with transplant-grade endothelium were mechanically injured with an 18-gauge cannula and a Fogla deep anterior lamellar keratoplasty dissector tip to create an easily identifiable "bullseye" pattern of cell death. Each cornea was then stained with trypan blue 0.06% for 90 seconds and imaged at 2× magnification. ACL on staining was measured using manual (ImageJ, National Institute of Health, Bethesda, MD) versus automated software tools (custom-built Aphelion macro, ADCIS, S.A., Saint-Contest, France). The bullseye was then imaged using specular microscopy, and ACL was measured by tracing the dead cell borders. ACL was then compared between both modalities. RESULTS: Eleven donor corneas were evaluated. Both manual (0.42 mm2) and automated (0.45 mm2) measurements of ACL after trypan staining underestimated mean ACL on specular imaging (0.54 mm2) (P < 0.01). However, on regression analysis, there was a good predictive correlation between automated trypan measurements and specular imaging (R2 = 0.99, residual SE = 0.0044, P < 0.01). When ACL on specular imaging was measured by tracing cell nuclei along the margin of injury (rather than cell borders) (0.45 mm2), there was no statistically significant difference between specular and automated trypan measurements (P = 0.95). CONCLUSIONS: Trypan-assisted automated measurements of ACL correlated well with ACL on specular imaging, suggesting that automated software may be a useful tool for evaluating endothelium in donor corneas.

Oral Miltefosine as Salvage Therapy for Refractory Acanthamoeba Keratitis.

PURPOSE: To report a case series of patients with treatment-resistant Acanthamoeba keratitis (AK) using oral miltefosine, often as salvage therapy. DESIGN: Descriptive, retrospective multicenter case series. METHODS: We reviewed 15 patients with AK unresponsive to therapy who were subsequently given adjuvant systemic miltefosine between 2011 and 2017. The main outcome measures were resolution of infection, final visual acuity, tolerance of miltefosine, and clinical course of disease. RESULTS: All patients were treated with biguanides and/or diamidines or azoles without resolution of disease before starting miltefosine. Eleven of 15 patients retained count fingers or better vision, and all were considered disease free at last follow-up. Eleven of 15 patients had worsening inflammation with miltefosine, with 10 of them improving with steroids. Six patients received multiple courses of miltefosine. Most tolerated oral miltefosine well, with mild gastrointestinal symptoms as the most common systemic side effect. CONCLUSIONS: Oral miltefosine is a generally well-tolerated treatment adjuvant in patients with refractory AK. The clinician should be prepared for a steroid-responsive inflammatory response frequently encountered during the treatment course.

Ex Vivo Safety and Efficacy of Paired Peripheral Incisions in Descemet's Membrane Endothelial Keratoplasty Grafts to Facilitate Unscrolling.

PURPOSE: To evaluate the ex vivo safety and efficacy of using paired peripheral incisions to achieve a triple scroll conformation that facilitates unscrolling in Descemet membrane endothelial keratoplasty (DMEK). METHODS: The safety of adding paired peripheral incisions to DMEK grafts was evaluated by assessing endothelial cell loss (ECL) and risk of tearing. ECL was measured using calcein-AM staining after incisions. The risk of tearing was evaluated by comparing incision lengths before and after simulated DMEK surgery using cadaveric eyes. Efficacy was evaluated by comparing the scrolling pattern and the width of grafts with different incision lengths (0.0 mm, 0.5 mm, and 1.0 mm). Surgical unscrolling times in simulated DMEK surgery by a novice DMEK surgeon were evaluated to determine whether incisions facilitate unscrolling in DMEK surgery. RESULTS: The mean ECL after adding incisions was 0.78% ± 0.23%. There was no significant change in incision length after simulated DMEK surgery (P = 0.6). In donor grafts aged less than or equal to 65 years, 60% (6/10) achieved a stable triple scroll with 0.5 mm incisions and 80% (8/10) achieved a stable triple scroll with 1.0 mm incisions. In donor grafts aged greater than 65 years, 0% (0/4) achieved a stable triple scroll. Mean graft width increased significantly after forming a triple scroll (5575 µm ± 1128 µm) compared with baseline (1563 µm ± 428 µm) (P < 0.001). In the hands of a novice DMEK surgeon, the mean unscrolling time was significantly shorter with incisions (2.61 min ± 1.41 min) versus without incisions (5.44 min ± 3.17 min) (P = 0.02). CONCLUSIONS: Paired peripheral incisions are safe and effective for inducing a triple scroll in DMEK grafts with donor age less than or equal to 65 years. Adding incisions may facilitate unscrolling for inexperienced DMEK surgeons.

Clinical and Histological Characterization of Toxic Keratopathy From Depatuxizumab Mafodotin (ABT-414), an Antibody-Drug Conjugate.

PURPOSE: To report the histological findings and clinical course of 2 patients with microcyst-like epithelial keratopathy (MEK) associated with antibody-drug conjugate, depatuxizumab mafodotin. METHODS: Case series. RESULTS: Two patients with glioblastoma multiforme participating in a phase 3 clinical trial of the antibody-drug conjugate, depatuxizumab mafodotin, presented with bilateral MEK. Confocal imaging showed multiple large, round, hyperreflective lesions in the epithelium. Epithelial debridement was performed for symptomatic relief in both patients. Along with aggressive lubrication, bandage contact lenses, and reduction in the chemotherapeutic dose to maintenance levels, both patients experienced symptomatic improvement. However, MEK lesions recurred after re-epithelialization. Immunohistochemistry of the diseased epithelium showed immunoglobulin (Ig)G-positive granular cytoplasmic inclusions and increased cell apoptosis. CONCLUSIONS: Depatuxizumab mafodotin accumulates in the basal corneal epithelium resulting in MEK because of increased apoptosis. Frequent lubrication and bandage contact lenses can provide symptom relief.

Characterization of Endothelial Cell Loss in Pre-Descemet Endothelial Keratoplasty Graft Preparation.

PURPOSE: To characterize the pattern and factors affecting endothelial cell loss (ECL) in pre-Descemet Endothelial Keratoplasty (PDEK) graft preparation. METHODS: A prospective study was performed to characterize the pattern of ECL and the impact of inflation pressure in PDEK. Donor corneas were randomized to inflation with air versus Optisol GS storage media. PDEK preparation was performed under continuous pressure monitoring. Trypan blue was used to grade the tissue as acceptable (<25% ECL) or unacceptable (≥25% ECL). Rate of unacceptable ECL was correlated with injection media type and inflation pressure. A retrospective study was then performed of all attempted PDEK preparations at Lions Gift of Sight to evaluate impact of donor tissue factors on ECL. Donor age and tissue preservation time were evaluated and correlated with ECL with PDEK bubbling. RESULTS: Twenty-five corneas were tested prospectively. A reticular pattern of ECL that varied in severity occurred with bubbling. There was no difference in peak inflation pressure or mean expansion pressure between air (706.0, 510.7 mm Hg) and Optisol GS (852.9, 653.0 mm Hg). Increasing peak inflation pressure and mean expansion pressure were associated with an increased risk for unacceptable ECL. On retrospective evaluation of 131 attempted PDEKs, only 44.0% of cases with successful bubbles had acceptable endothelium after processing. Increasing donor age and decreasing preservation time were associated with increased rates of acceptable endothelium. CONCLUSIONS: PDEK processing can result in a reticular pattern of ECL. Higher inflation pressures are associated with greater ECL. Older donor tissues with shorter preservation times might be preferable for PDEK.

Immunohistochemical Study of SARS-CoV-2 Viral Entry Factors in the Cornea and Ocular Surface.

PURPOSE: To confirm the ocular tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by evaluating the expression of viral entry factors in human ocular tissues using immunohistochemistry. METHODS: Fresh donor corneas and primary explant cultures of corneal, limbal, and conjunctival epithelial cells were evaluated for the expression of viral entry factors. Using immunohistochemistry, the samples were tested for the expression of angiotension-converting enzyme 2 (ACE2), dendritic cell-specific intracellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN), DC-SIGN-related protein (DC-SIGNR), and transmembrane serine protease 2 (TMPRSS2). RESULTS: In total, 5 donor corneas were evaluated for the expression of viral entry factors. In all specimens, both ACE2 and TMPRSS2 were expressed throughout the surface epithelium (corneal, limbal, and conjunctival) and corneal endothelium. In corneal stromal cells, ACE2 was sporadically expressed, whereas TMPRSS2 was absent. DC-SIGN/DC-SIGNR expression varied between donor specimens. Four specimens expressed DC-SIGN/DC-SIGNR in a similar distribution to ACE2, but 1 specimen from a young donor showed no expression of DC-SIGN/DC-SIGNR. ACE2, TMPRSS2, and DC-SIGN/DC-SIGNR were all expressed in the cultured corneal, limbal, and conjunctival epithelial cells. CONCLUSIONS: Both corneal and conjunctival epithelia express ACE2, DC-SIGN/DC-SIGNR, and TMPRSS2, suggesting that the ocular surface is a potential route for the transmission of SARS-CoV-2. The risk of viral transmission with corneal transplantation cannot be ruled out, given the presence of ACE2 in corneal epithelium and endothelium. Cultured corneal, limbal, and conjunctival epithelial cells mimic the expression of viral entry factors in fresh donor tissue and may be useful for future in vitro SARS-CoV-2 infection studies.

Peripheral Endothelial Cell Density in Descemet Membrane Endothelial Keratoplasty Grafts.

PURPOSE: To compare the variation in corneal endothelial cell density (ECD) from the center to the periphery in unpeeled and peeled donor corneas and to determine the impact of eccentric trephining on total endothelial cells in Descemet membrane endothelial keratoplasty (DMEK) grafts. METHODS: Mated donor cornea pairs were obtained. One cornea from each pair was peeled for DMEK, whereas the other was left unpeeled. Alizarin Red was used to stain the endothelial cells. High-resolution images at fixed magnification were obtained for the center, midperiphery (2.5 mm from the center), and the periphery (5 mm from the center). The cells were then counted, and ECD was calculated by a masked evaluator using ImageJ software. Regression analysis was then performed to evaluate the change in ECD as a function of radius (distance from the corneal center). The impact of eccentric trephining on total endothelial cells in a given DMEK graft was then calculated using numerical integration. RESULTS: Ten pairs of corneas were evaluated. ECD increased by 1.4% (40.0 cells/mm) (P = 0.03) for peeled corneas and 1.8% (51.5 cells/mm) (P < 0.01) for unpeeled corneas for each millimeter from the center. There was no difference between peeled and unpeeled corneas in the mean central (P = 0.98) or peripheral (P = 0.35) ECD. Based on the increase in ECD as a function of radius, eccentric trephining of a 7.5-mm DMEK graft by 2.25 mm yields 0.95% more total endothelial cells per graft. CONCLUSIONS: Corneal ECD increases from the center to the periphery in both peeled and unpeeled corneas. Eccentric trephining increases the number of transplanted endothelial cells per graft.

Endothelial dysfunction in a child with Pearson marrow-pancreas syndrome managed with Descemet stripping automated endothelial keratoplasty using a suture pull-through technique.

A 4-year-old girl with a history of Pearson marrow-pancreas syndrome presenting with severe, progressive photophobia was found to have bilateral, diffuse corneal thickening and peripheral pigmentary retinopathy. She underwent Descemet stripping automated endothelial keratoplasty (DSAEK) surgery in both eyes using a modified suture pull-through technique. Postoperatively there was no evidence of cataract formation or graft detachment; her corneas thinned, and her photophobia improved dramatically.

Case Report: Penetrating Corneal Injury Under an Intact Laser-assisted in Situ Keratomileusis Flap.

SIGNIFICANCE: As the prevalence of post-laser-assisted in situ keratomileusis (LASIK) patients rises, recognition of possible traumatic complications and their management in this population becomes increasingly relevant. Penetrating injuries and intraocular foreign bodies are possible in post-LASIK corneas despite an intact anterior corneal surface. However, with prompt recognition and treatment, excellent visual recovery can be achieved. PURPOSE: The purpose of this study was to report an interesting case of a penetrating foreign body through an intact LASIK flap. CASE REPORT: A 48-year-old man presented to an outside provider with right eye pain after his eye was struck by a tree branch. His ocular history was notable for uncomplicated LASIK surgery 4 years before presentation. On initial examination, the patient was diagnosed as having a small corneal abrasion and hyphema. Despite appropriate therapy, his eye continued to subjectively and objectively worsen. Follow-up examination after the injury was notable for a new dense hypopyon. Because of concern for secondary infection, the patient was referred urgently for further evaluation. Upon referral, the patient was noted to have a dense, fibrinous mass located inferiorly in the anterior chamber. Although the cornea was edematous temporally with deep folds, the anterior corneal surface appeared intact without evidence of laceration or flap displacement. Concern for endophthalmitis prompted anterior chamber washout, where a large vegetative foreign body was recovered despite an intact anterior corneal surface and LASIK. Post-operative anterior-segment optical coherence tomography after resolution of the corneal edema confirmed the presence of a well-aligned penetrating tract through the posterior stromal bed underneath the LASIK flap. Epithelial ingrowth that developed within the post-operative period further affirmed the initial tract of the penetrating foreign body. CONCLUSIONS: This case illustrates a novel complication after trauma in a post-LASIK patient, describes possible management, and underscores the care that must be taken when assessing patients with a history of LASIK surgery.

Clinical and Histological Characterization of Toxic Keratopathy From Depatuxizumab Mafodotin (ABT-414), an Antibody-Drug Conjugate: [RETRACTED].

PURPOSE: To report the first histological characterization of microcyst-like epithelial keratopathy (MEK) associated with depatuxizumab mafodotin (ABT-414). METHODS: Case report. RESULTS: A 35-year-old man with glioblastoma multiforme participating in a phase III trial of the antibody-drug conjugate ABT-414 developed a large corneal abrasion from complications of MEK. Confocal imaging showed multiple large, round, hyperreflective lesions. Epithelial debridement was performed. Immunohistochemistry of the diseased epithelium showed IgG-positive granular cytoplasmic inclusions and increased cell apoptosis. With discontinuation of topical steroids, frequent lubrication, bandage contact lenses, and reduction in dose to maintenance therapy, the patient experienced symptomatic improvement. However, the MEK lesions recurred after debridement. CONCLUSIONS: ABT-414 accumulates in the basal corneal epithelium resulting in MEK due to increased apoptosis. Frequent lubrication and bandage contact lenses can provide symptom relief.

Technique for Preparing Ultrathin and Nanothin Descemet Stripping Automated Endothelial Keratoplasty Tissue.

PURPOSE: To describe and report outcomes of our single-pass microkeratome technique for preparation of ultrathin (UT, ≤100 µm) and nanothin (NT, ≤50 µm) Descemet stripping automated endothelial keratoplasty (DSAEK) grafts. METHODS: To prepare NT-DSAEK grafts, a pachymetry nomogram specific to each technician and individual microkeratome head was developed based on accumulated precut and postcut pachymetry data from previous DSAEK grafts. Mean graft thickness as well as precut and postcut endothelial cell counts (ECCs) of NT-DSAEK, UT-DSAEK, and Descemet membrane endothelial keratoplasty (DMEK) grafts between July 2015 and July 2017 were calculated and compared statistically. Endothelial cell loss was evaluated using calcein AM stains and ImageJ analysis. Postcut graft thickness and rates of perforation/tissue loss for NT-DSAEK grafts between May and July 2017 were calculated to determine overall graft preparation success rates. RESULTS: Mean postcut graft thickness for all grafts within the NT range was 41.0 ± 6.4 µm (range 26-50 µm). Mean ECC did not differ between NT-DSAEK, UT-DSAEK, and DMEK grafts (P = 0.759 and 0.633, respectively). The overall tissue loss rate from attempted NT-DSAEK was 4.8%. Excluding cases of perforation, the chance of achieving NT thickness was 60% and within the traditional UT range was 100%. CONCLUSIONS: We propose the term "NT-DSAEK" for grafts ≤50 µm. The described nomogram allows for standardized creation of NT grafts with a low tissue loss rate. This technique is safe and does not result in significant ECC loss compared with UT-DSAEK and DMEK grafts. Further studies are necessary to corroborate the postsurgical results of NT grafts.