Presence of Panel-reactive Antibodies after Penetrating Keratoplasty.

PURPOSE: To evaluate the relationship between penetrating keratoplasty (PK) and postoperative PRA level and number of unacceptable antigens. METHODS: A cross-sectionalstudy was performed on patients with history of PK. Patients with prior solid organ transplantation, pregnancy, or blood transfusion were excluded. These findings were combined with a retrospective review. Patients were grouped by single or multiple PKs. The primary outcome was postoperative PRA level. RESULTS: Incidence of postoperative PRA elevation and mean peak PRA was higher in the multiple PK group (p = .08 and p = .010, respectively). Mean number of unacceptable antigens was elevated in the multiple PK group (p = .024). There was a moderately positive correlation between number of PK grafts and PRA level (r = 0.629, p = .0002). CONCLUSIONS: PRA level may be influenced by PKs, with higher PRA associated with increased prior PKs. Further studies are necessary to determine the potential prognostic value.Abbreviations: PK: penetrating keratoplasty; PRA: panel reactive antibodies; OSST: ocular surface stem cell transplantation; LSCD: limbal stem cell deficiency.

Clinical Outcomes of Allogeneic Ocular Surface Stem Cell Transplantation in Pediatric Patients.

PURPOSE: To describe the outcomes of allograft ocular surface stem cell transplantation (OSST) and the complication profile of systemic immunosuppression (SI) in pediatric patients with limbal stem cell deficiency. METHODS: This was a retrospective interventional case series from a single tertiary referral institution of 20 eyes from 13 patients who 1) underwent allograft OSST surgery, 2) were 18 years or less at time of OSST, and 3) received SI with 4) a minimum of 12-months follow-up. The main outcome measures were ocular surface stability, visual acuity, and SI adverse events. RESULTS: The mean age of patients was 15.1 ± 3.2 years (range 9-18 years). The mean follow-up was 5.6 ± 5.0 years after OSST. At the last follow-up, 15 eyes (75%) had a stable ocular surface, 1 eye (5%) developed partial failure, and 4 eyes (20%) developed total surface failure. Preoperative mean logarithm of the minimum angle of resolution visual acuity 1.5 improved to 1.1 at the last follow-up (P = 0.1); when 4 eyes of 3 nonadherent patients were excluded, the results were more pronounced and statistically significant (1.5 improved to 1.0, P = 0.002). SI was tolerated well by all patients with minimal adverse events. CONCLUSIONS: OSST provides a stable ocular surface and is a successful treatment option for pediatric patients with limbal stem cell deficiency. SI is well-tolerated with a minimal complication profile.

"Basket" mattress suture to manage positive vitreous pressure during penetrating keratoplasty.

OBJECTIVE: To describe a new/modified technique to manage posterior vitreous pressure (PVP) during penetrating keratoplasty (PKP) and report a small series. DESIGN: Retrospective interventional case series and technique description. PARTICIPANTS: PKP eyes necessitating mattress suture placement owing to PVP. METHODS: Retrospective chart review from 2016 to 2019 was undertaken. Placed prophylactically (before trephination) or after trephination, the mattress suture is placed limbus-to-limbus across the anterior chamber. A second mattress suture can be placed in the opposite meridian (perpendicularly) for added support (safety basket configuration). Variations of suture technique are described based on lens status (i.e., phakic, pseudophakic, aphakic) and intraoperative timing. Parameters assessed included demographics, lens status, suture indications, intraoperative technique details, successful PKP completion, and presence of primary failure. RESULTS: There were 6 phakic eyes (5 patients) and 9 pseudophakic/aphakic eyes (8 patients). Indications for the phakic subgroup were obesity (83%), poor scleral rigidity (83%), repeated iris prolapse (67%), dense mature cataract (33%), and planned large-diameter PKP (33%). Indications for pseudophakic/aphakic eyes included intraocular lens/iris prolapse (100%), pre-existing iris defects (67%), and planned large-diameter PKP (33%). Successful PKP was performed in all cases. Whereas one case had residual corneal edema in the setting of a persistent epithelial defect owing to limbal stem cell deficiency, all other cases demonstrated no primary graft failure. CONCLUSIONS: Although increased PVP can present a stressful and challenging situation, it is important to have multiple options for management. This simple mattress suture technique normalizes the lens-iris complex behaviour and appears safe for the donor graft.

Long-term Outcomes of Living-Related Conjunctival Limbal Allograft Compared With Keratolimbal Allograft in Patients With Limbal Stem Cell Deficiency.

PURPOSE: To compare the long-term outcomes of living-related conjunctival limbal allograft (lr-CLAL) with keratolimbal allograft (KLAL) in patients with limbal stem cell deficiency. METHODS: A retrospective, comparative, interventional cohort of patients with bilateral total limbal stem cell deficiency who underwent surgical treatment with a KLAL or lr-CLAL procedure alone (not combined with any other ocular surface stem cell transplantation procedures) with a minimum follow-up of 1 year and who received systemic immunosuppression. Ocular surface stability, best-corrected visual acuity (BCVA), and postoperative complications at the last follow-up were the main outcome measures. RESULTS: There were 224 eyes that underwent KLAL alone and 63 eyes that underwent lr-CLAL alone, with a mean follow-up time for all eyes of 7.2 years (range 1.0-16.0 years). For lr-CLAL eyes, 82.5% maintained a stable ocular surface compared with 64.7% of KLAL eyes at the last follow-up. Only 6.3% of lr-CLAL eyes demonstrated a failed ocular surface compared with 15.6% of KLAL eyes. The mean BCVA was 20/158 for KLAL eyes compared with 20/100 for lr-CLAL eyes at the last follow-up. A smaller proportion of lr-CLAL eyes (30.2% compared with 43.3%) developed an episode of acute rejection, and a higher proportion of these episodes resolved with treatment in the lr-CLAL group (79.0% compared with 53.6%). CONCLUSIONS: lr-CLAL demonstrates lower rejection rates, improved graft survival, and better BCVA compared with KLAL. Both careful preoperative donor selection and triple-agent systemic immunosuppression (including tapered systemic corticosteroids) are critical to optimizing the ocular surface stem cell transplantation outcomes.

Amniotic Membrane Transplantation in Acute Severe Ocular Chemical Injury: A Randomized Clinical Trial.

PURPOSE: To compare the outcomes of conventional medical treatment vs combined medical treatment and amniotic membrane transplantation (AMT) in the management of patients with Roper-Hall grade IV ocular chemical injury. DESIGN: Randomized, parallel-controlled clinical trial. METHODS: Setting: Single tertiary referral hospital. PATIENTS: Sixty eyes of 60 patients with Roper-Hall grade IV ocular chemical injury with a minimum follow-up of 12 months were enrolled in the study. INTERVENTION: Patients were randomly assigned to 2 groups: Group 1 (30 eyes) received topical preservative-free lubricating gel and drops, chloramphenicol, betamethasone, homatropine, oral vitamin C, and doxycycline; Group 2 (30 eyes) received amniotic membrane transplant (AMT) on the entire ocular surface in addition to the medical treatment provided in Group 1. OUTCOME MEASURES: The main outcome measure was time to complete corneal epithelialization. Secondary outcome measures were best-corrected visual acuity (BCVA) and neovascularization in the central 5 mm of the cornea. RESULTS: Mean follow-up time was 20.3 ± 2.5 months (range 13-24 months). Corneal epithelial defects healed within 72.6 ± 30.4 (21-180) days in Group 1 vs 75.8 ± 29.8 (46-170) days in Group 2 (P = .610). Mean BCVA was 2.06 ± 0.67 (0.4-2.6) logMAR vs 2.06 ± 0.57 (1-2.9) logMAR in Groups 1 and 2, respectively (P = .85). Group 1 developed more central corneal neovascularization (22 eyes; 73.3%) compared to Group 2 (16 eyes; 53.3%); however, it was not statistically significant (P = .108). CONCLUSIONS: In comparison to conventional medical therapy, combined amniotic membrane transplantation and medical therapy does not accelerate corneal epithelialization or affect final visual acuity in severe chemical injuries.

Management of advanced ocular surface disease in patients with severe atopic keratoconjunctivitis.

AIM & OBJECTIVE: Severe ocular surface disease, including limbal stem cell deficiency (LSCD) can occur as a consequence of severe atopic keratoconjunctivitis (AKC) that has been inadequately treated. Our goal was to describe the management and outcomes of severe ocular surface disease in AKC patients. METHODS: We performed a retrospective analysis of a case series of 13 eyes of 8 patients with advanced ocular surface disease associated with severe AKC. The clinical presentation, medical and surgical management, and visual and anatomic outcomes were analyzed. RESULTS: Five eyes were treated with medical interventions alone, which included topical or systemic immunomodulatory therapy (IMT) for all eyes. These eyes had a decline in mean visual acuity from LogMAR 0.96 to 2.04 between the initial and final visits related to recurrent epithelial defects or corneal ulceration. Eight eyes were treated with surgical approaches in addition to medical treatment. Initial surgical treatments included limbal stem cell transplantation (n = 5), Boston keratoprosthesis (n = 2), and superficial keratectomy (n = 1). Both eyes that underwent primary keratoprosthesis had severe post-operative complications and became no light perception. In the remainder of the surgically treated eyes, there was an improvement visual acuity from LogMAR 1.43 to 0.6 between the pre-operative and final post-operative visit. CONCLUSION: Visual rehabilitation in eyes severe ocular surface disease due to prolonged AKC is challenging. While some patients did experience improved vision, most eyes did not improve or experienced severe complications with vision loss. Early intervention with immunomodulatory therapy may prevent progression of the disease to advanced stages.

Ocular Surface Stem Cell Transplantation for Treatment of Keratitis-Ichthyosis-Deafness Syndrome.

PURPOSE: To report our surgical experience with ocular surface stem cell transplantation (OSST) for limbal stem cell deficiency (LSCD) in the setting of keratitis-ichthyosis-deafness (KID) syndrome. METHODS: Retrospective interventional case series. RESULTS: We present 5 eyes of 3 patients with KID syndrome that developed LSCD and underwent OSST. Mean follow-up after OSST was 8.3 ± 4.3 years (range 3.4-11.4 years). Two eyes underwent living-related conjunctival limbal allograft (lr-CLAL), and 3 eyes were treated with keratolimbal allograft (KLAL). Four of the 5 eyes underwent subsequent keratoplasty. Both lr-CLAL eyes maintained a stable ocular surface at final follow-up. Conversely, all KLAL eyes developed a failed surface requiring repeat KLAL surgery. Because of multiple failed KLALs, 1 eye underwent placement of a keratoprosthesis. CONCLUSIONS: KID syndrome is a rare cause of LSCD. Although OSST can stabilize the surface, long-term treatment of KID syndrome can be challenging. An lr-CLAL may offer further benefit over a KLAL in these eyes because it is HLA- and ABO-matched tissue; it also helps to treat keratoconjunctivitis sicca, often a prominent feature of KID syndrome.

Infectious Keratitis After Ocular Surface Stem Cell Transplantation.

PURPOSE: To describe the rate, clinical/microbiological characteristics, and outcomes of infectious keratitis in eyes with limbal stem cell deficiency after ocular surface stem cell transplantation (OSST). METHODS: In this retrospective chart review of 278 eyes that underwent OSST between January 2006 and December 2016, eyes treated for previous infectious keratitis (bacterial, fungal, or viral) were included. Demographics, risk factors, course, microbiological characteristics, and outcomes were assessed. RESULTS: A total of 52 eyes (18.7%) of 48 patients (28 men and 20 women) developed 75 episodes (culture-proven or presumed) of infectious keratitis (range 1-4 episodes) with mean follow-up of 5.3 ± 3.6 years after OSST. The most common limbal stem cell deficiency etiologies included chemical/thermal (27 episodes), Stevens-Johnson syndrome (19 episodes), aniridia (8 episodes), and mucous membrane pemphigoid (8 episodes). There were 44 (58.7%) bacterial keratitis episodes, 24 (32%) fungal keratitis episodes, and 7 (9.3%) HSV keratitis episodes. Gram-positive bacteria (79%) and Candida species (73%) were the most common bacterial and fungal pathogens. Before infection, 33% had an epithelial defect, 69% had a bandage contact lens, 91% were on systemic immunosuppression, and 25% recently had undergone ocular surgery (<3 months). Although 75% resolved with antimicrobial treatment, 25% required a therapeutic keratoplasty (TPK; 2 cases needed multiple TPK). CONCLUSIONS: Despite successful OSST surgery, infectious keratitis is relatively common, and aggressive medical/surgical therapy is warranted. Prophylactic topical antibiotics and a cicatrizing conjunctivitis diagnosis may account for the high proportion of fungal keratitis in this population.

Comparison of Visual Acuity Outcomes Between Nanothin Descemet Stripping Automated Endothelial Keratoplasty and Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To compare the visual outcomes and complications between nanothin Descemet stripping automated endothelial keratoplasty (NT-DSAEK) and Descemet membrane endothelial keratoplasty (DMEK). METHODS: A prospective comparative case series of 28 consecutive cases of NT-DSAEK (less than or equal to 50 µm) and DMEK was undertaken. Inclusion criteria were a diagnosis of Fuchs dystrophy, presence of pseudophakia, or planned combined cataract surgery/endothelial keratoplasty, with a minimum of 6-month follow-up. Exclusion criteria were any concurrent ocular comorbidities. Primary outcomes measures were best spectacle-corrected visual acuity (BSCVA) and complications. RESULTS: Mean thickness of NT-DSAEK grafts was 41.0 ± 7.5 µm (range 26-50 µm). At 1 month postoperatively, the DMEK group had significantly better mean BSCVA of 0.18 ± 0.20 logarithm of the minimum angle of resolution (logMAR) (20/33) compared with 0.28 ± 0.16 logMAR (20/40) for NT-NSAEK (P = 0.049). At 3, 6, and 12 months postoperatively, mean BSCVA was comparable between both groups [3 months: NT-DSAEK 0.17 ± 0.12 logMAR (20/30) versus DMEK 0.13 ± 0.17 (20/27), P = 0.31; 6 months: NT-DSAEK 0.11 ± 0.10 logMAR (20/26) versus DMEK 0.09 ± 0.10 (20/25), P = 0.63; 12 months: NT-DSAEK 0.07 ± 0.09 logMAR (20/24) versus DMEK 0.07 ± 0.11 logMAR (20/24), P = 0.95]. Other than 1 NT-DSAEK graft that was successfully rebubbled, no other complications were encountered in either group. CONCLUSIONS: Compared with DMEK, NT-DSAEK provides comparable visual outcomes and complications rates.

Cincinnati Protocol for Preoperative Screening and Donor Selection for Ocular Surface Stem Cell Transplantation.

PURPOSE: To describe our process for preoperative screening and donor selection for ocular surface stem cell transplantation (OSST). METHODS: A 7-year retrospective chart review was performed on limbal stem cell deficiency patients. The inclusion criterion was all patients who underwent an OSST procedure. The exclusion criterion was eyes with unilateral disease in which an autograft was performed. Data for human leukocyte antigen (HLA) typing, virtual crossmatching, donor-specific antibody, and panel reactive antibody level were obtained. RESULTS: Of the included 142 eyes (104 patients), 19 patients had no recorded living donor availability data, and HLA typing was not performed on 16 patients. A total of 94 donors (mean 1.4 donors/patient, range 1-6) were tested for 67 recipients. For 2 patients with graft-versus-host disease, no further HLA typing was needed, as the donors were known HLA-identical donors. For 47 patients, only 1 donor was tested, whereas multiple donors underwent HLA typing for 20 patients. There were 73 ABO (blood group)-compatible matches for the 61 tested recipients, and only 1 recipient did not have any ABO-compatible donor. For the virtual crossmatch, there were 5 patients who did not have a compatible donor (positive virtual crossmatch). The best available donor match was a sibling for 41 recipients (65%), a parent for 19 recipients (30%), and an offspring for 3 recipients (5%). CONCLUSIONS: Our protocol for OSST preoperative screening and donor selection minimizes the antigenic burden for transplanted tissue by selecting the best available donor match.

Three Hundred Sixty-Degree Fuchs Superficial Marginal Keratitis Managed With Annular Lamellar Keratoplasty.

PURPOSE: To report a case of extensive Fuchs superficial marginal keratitis managed with annular lamellar keratoplasty. METHODS: Interventional case report. RESULTS: A 72-year-old man presented with 20/80 best-corrected visual acuity in his left eye and demonstrated 360-degree peripheral deep immune stromal keratitis and pseudopterygia with peripheral stromal thinning. During superficial keratectomy with amniotic membrane transplantation, the thin cornea was perforated while excising pseudopterygia in the superonasal quadrant. Surgery was aborted. Anterior segment optical coherence tomography demonstrated a severely thinned cornea (240 µm nasally, 360 µm temporally) with overlying pseudopterygia peripherally. After allowing 3 months for the cornea to heal, the decision was made to perform lamellar annular (or "donut") keratoplasty. The patient had an unremarkable postoperative course, with 20/50 best-corrected visual acuity 10 months after keratoplasty. CONCLUSIONS: We report an extensive case of Fuchs superficial marginal keratitis treated with 360-degree annular lamellar keratoplasty. This technique provides tectonic support to decrease the likelihood of future perforation while also improving vision by modifying the ectatic cornea. Anterior segment optical coherence tomography may be a helpful tool preoperatively to avoid severely thinned areas (eg, during pseduopterygium removal) and to ensure complete removal of the ectatic cornea.

Microarray analysis identifies changes in inflammatory gene expression in response to amyloid-beta stimulation of cultured human retinal pigment epithelial cells.

PURPOSE: Age-related macular degeneration (AMD) is a common cause of irreversible vision loss in the elderly. The hypothesis was that in vitro stimulation of RPE cells with Abeta(1-40), a constituent of drusen, promotes changes in gene expression and cellular pathways associated with the pathogenesis of AMD, including oxidative stress, inflammation, and angiogenesis. METHODS: Confluent human RPE cells were stimulated with Abeta(1-40), or the reverse peptide Abeta(40-1), and genome wide changes in gene expression were studied with gene microarrays. Selected genes were verified by qRT-PCR and ELISA. Pathway analysis with gene set enrichment analysis (GSEA) and ingenuity revealed top functional pathways in RPE after Abeta(1-40) stimulation. RESULTS: RPE cells stimulated with Abeta(1-40) (0.3 microM) for 24 hours resulted in 63 upregulated and 22 downregulated previously known genes. The upregulated genes were predominantly in inflammatory and immune response categories, but other categories were also represented, including apoptosis, cell signaling, cell proliferation, and signal transduction. Categories of downregulated genes included immune response, transporters, metabolic functions and transcription factors. ELISA confirmed that secreted levels of IL-8 were two times higher than control levels. GSEA and ingenuity analysis confirmed that the top affected pathways in RPE cells after Abeta(1-40) stimulation were inflammation and immune response related. Surprisingly, few angiogenic pathways were activated at the doses and exposure times studied. CONCLUSIONS: Abeta(1-40) promotes RPE gene expression changes in pathways associated with immune response, inflammation, and cytokine and interferon signaling pathways. Results may relate to in vivo mechanisms associated with the pathogenesis of AMD.