Ocular Mucous Membrane Pemphigoid: The Effect of Risk Factors at Presentation on Treatment Outcomes.

PURPOSE: Analyze the influence of risk factors at presentation in the long-term immunosuppressive therapy (IMT) outcomes of ocular mucous membrane pemphigoid (OMMP). DESIGN: Retrospective multicenter study. PARTICIPANTS: Patients with OMMP seen at the Duke Eye Center, Tecnologico de Monterrey, and Hospital Clinic of Barcelona from 1990 to 2022. METHODS: Data at presentation on demographics, direct immunofluorescence, ocular findings, sites of extraocular manifestations (EOMs), and previous treatments in patients with a clinical or laboratory diagnosis of OMMP, were analyzed with multivariable analysis and Kaplan-Meier plots to identify factors associated with adverse outcomes. MAIN OUTCOME MEASURES: (1) Inflammatory control (no conjunctival inflammation in both eyes at 3 months on IMT); (2) relapse (new-onset inflammation after absolute control in either eye); (3) progression (≥ 1 cicatrizing stage progression in either eye); and (4) vision loss (≥ 2 Snellen lines). RESULTS: A total of 117 patients (234 eyes), 61% (71/117) of whom were women, with a mean age of 66.6 (SD: 12.4) years (range: 37-97 years) and median follow-up of 34 months (interquartile range: 16-66 months; range: 3-265 months), were enrolled. Inflammatory control was achieved in 57% of patients (67/117), with high-risk EOM (HR-EOM), including esophageal, nasopharyngeal, and/or genital involvement (adjusted odds ratio [aOR]: 12.51; 95% confidence interval [CI]: 2.61-59.99; P = 0.002) and corneal scarring (aOR: 3.06; 95% CI, 1.15-8.14; P = 0.025), as significant risk factors for persistent inflammation. Disease relapse, progression, and vision loss occurred in 20% of patients (23/117), 12% of patients (14/117), and 27% of patients (32/117), respectively. Baseline corneal scarring was a risk factor for relapse (adjusted hazard ratio: 4.14; 95% CI: 1.61-10.62; P = 0.003), progression (aOR: 11.46; 95% CI: 1.78-73.75; P = 0.010), and vision loss (aOR: 3.51; 95% CI: 1.35-9.10; P = 0.010). HR-EOM was associated with stage progression (aOR, 34.57; 95% CI, 6.57-181.89; P<0.001) and vision loss (aOR, 8.42; 95% CI, 2.50-28.42; P = 0.001). No significant differences were found between IMT regimes and relapse (P = 0.169). CONCLUSIONS: Ocular mucous membrane pemphigoid presenting with HR-EOMs and corneal scarring has an increased risk of stage progression and vision loss. Corneal scarring and severe inflammation at baseline were associated with an increased risk of relapse. A disease progression staging system incorporating both the HR-EOMs and corneal involvement is required to predict the visual outcome of OMMP better. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Incidence, risk factors, and treatment of retroprosthetic membranes following Boston keratoprosthesis eyes and the impact of glaucoma surgery.

PURPOSE: To assess incidence, risk factors, and treatment of retroprosthetic membrane (RPM) formation in eyes following Boston keratoprosthesis (Kpro) implantation and their correlation with glaucoma drainage device placement (GDD). METHODS: A retrospective review was performed on eyes that underwent Kpro type I or II implantation between 2005 and 2020 at a tertiary academic center. Multiple variables were collected including preoperative characteristics, presence of RPM, management of RPM, and outcomes including corrected visual acuity (VA). A Fischer's exact test was used to evaluate the significance of risk factors of RPM formation and an odds ratio was calculated for each possible risk factor. A Mann-Whitney U test was used to evaluate comparisons between outcomes and qualitative analyses. RESULTS: Of the 87 eyes identified, 37 (43%) developed an RPM within an average of 1.5 years (range, 31 days-7.5 years) following Kpro implantation. Mean follow-up duration was 4.3 years. Eyes that developed RPM had significantly worse preoperative VA compared to those that did not (logMAR 2.55 vs. 2.28, p = 0.022). The mean number of prior penetrating keratoplasty procedures trended higher in eyes that developed RPM (2.46 vs. 2.18, p = 0.44) but was not significant. GDD placement after Kpro implantation was associated with an increased risk of RPM formation (RR = 1.69 p = 0.026). Of the 37 eyes that developed an RPM following Kpro, 17 (47%) were treated with Nd:YAG laser, and four of those 17 (21%) also underwent pars plana vitrectomy (PPV). Seven of 37 eyes (19%) underwent PPV without Nd:YAG. Comparisons between RPM occurrence and final VA were not significant. CONCLUSIONS: The incidence of RPM formation following Kpro implantation was 43%. Eyes that developed RPM had significantly worse preoperative VA. GDD placement after Kpro implantation increased the risk of developing RPM. Final VA and occurrence of RPM were not significantly different between the Nd:YAG and PPV treatment groups.

Case Series of Patients With Hereditary Benign Intraepithelial Dyskeratosis.

PURPOSE: The purpose of this retrospective case series was to compare the outcomes of different treatment options for patients diagnosed with hereditary benign intraepithelial dyskeratosis (HBID). METHODS: The study is designed as a single-institution retrospective chart review of patients who were clinically diagnosed with HBID during their care at the Duke Eye Center. Patient demographics were obtained, and disease course after different therapies was analyzed. RESULTS: Seventeen patients were diagnosed with HBID. 52.9% (9/17) of patients identified with HBID reported Native American ancestry. Medical therapy alone failed to reduce the size or number of corneal lesions in any patient identified in this study. Ten of the 17 patients required surgical intervention. Two eyes received corneal biopsies, 3 eyes received a full conjunctival lesion excision with amniotic membrane grafting, 12 eyes received superficial keratectomy with amniotic membrane grafting, and 1 eye received keratoprosthesis. Lesion recurrence was seen in 9 of the 10 patients treated with surgical excision with an average time to recurrence of 1.5 and 2 months for conjunctival excisions and superficial keratectomy, respectively, when excluding patients who missed scheduled postoperative follow-up appointments. CONCLUSIONS: Hereditary benign intraepithelial dyskeratosis is a rare and poorly understood disorder that predominantly affects people with Native American ancestry. Medical therapy only provides symptomatic relief, and patients who receive surgical excision almost always develop recurrence. As a result, we recommend future investigations focus on identifying the optimal surgical technique and timing to limit the morbidity of HBID and improve outcomes.

A Randomized Trial of Topical Fibrinogen-Depleted Human Platelet Lysate Treatment of Dry Eye Secondary to Chronic Graft-versus-Host Disease.

Purpose: The purpose of the study was to evaluate, as a pilot trial, safety and tolerability of CAM-101 10% and 30% topical ophthalmic fibrinogen-depleted human platelet lysate (FD hPL) solution in patients with dry eye disease (DED) secondary to graft-versus-host disease (GvHD) after 6 weeks of treatment. Design: A phase I/II, pilot, prospective, multicenter, randomized, double-masked clinical trial. Participants: Patients with DED secondary to GvHD. Methods: Sixty-four adult patients were stratified by "symptom severity" (Ocular Surface Disease Index [OSDI], ocular discomfort Visual Analog Scale (VAS), ocular symptom frequency, and use of artificial tears) and then randomized 1:1:1 to CAM-101 (FD hPL) at 10% or 30% concentration or an electrolyte (Plasma-Lyte A) vehicle control, 1 drop in both eyes, 4 times daily, for 42 days. After 42 days, control patients were offered 42 days of open-label treatment with 30% FD hPL. Main Outcome Measures: Primary outcome safety measures were ocular and systemic adverse events and the number of patients in each group with clinically significant change from normal to abnormal in any ocular findings. Secondary outcomes were changes from baseline to day 42 in ocular discomfort, OSDI, fluorescein corneal staining, and lissamine green conjunctival staining relative to the vehicle control. The ocular symptom frequency was assessed on a 100-point VAS. Results: FD hPL 10% and 30% were safe and well tolerated. Relative to the vehicle control, significant decreases from baseline to day 42 were seen in the FD hPL 30% group with regard to ocular discomfort (mean decrease = -18.04; P = 0.018), frequency of burning/stinging (-20.23; P = 0.022), eye discomfort (-32.97; P < 0.001), eye dryness (-21.61; P = 0.020), pain (-15.12; P = 0.044), photophobia (-24.33; P = 0.0125), and grittiness (-20.08; P = 0.0185). Decreases were also seen for itching and foreign body sensation, though not statistically significant. Improvements were seen in tear breakup time (mean increase = 1.30 seconds; P = 0.082) and the investigator's global evaluation 4-point scale (mean decrease = -0.86; P = 0.026). Corneal fluorescein staining was not improved. The OSDI had a mean decrease of -8.88 compared to the vehicle, although not statistically significant. Conclusions: Fibrinogen-depleted human platelet lysate appears to be well tolerated, with no significant toxicity at concentrations of 10% and 30%. These initial data suggest some efficacy, especially for subjective outcome measures relative to baseline assessments and treatment with the vehicle, but larger studies are needed to confirm these effects.

CLINICAL CHARACTERISTICS AND VISUAL OUTCOMES IN ENDOPHTHALMITIS AFTER KERATOPROSTHESIS IMPLANTATION.

PURPOSE: To describe the presentation, microbiology, management, and prognosis of eyes with endophthalmitis after Boston keratoprosthesis implantation. METHODS: Retrospective case series with history, diagnostics, management, and outcomes data in endophthalmitis after keratoprosthesis implantation presenting to a tertiary center between 2009 and 2020. RESULTS: Of 137 keratoprosthesis-implanted eyes, 7 eyes of 7 patients (5%) developed endophthalmitis. On presentation, 6 (86%) reported decreased visual acuity, and only 1 (14%) reported pain. Peripheral corneal ulcers were present in 2 eyes (29%). Seidel testing was negative in all cases. Six eyes (86%) had retroprosthetic membranes. One (14%) underwent initial pars plana vitrectomy with mechanical vitreous biopsy, whereas 6 (86%) received a needle vitreous tap-half of which were dry. Organisms were isolated after vitreous tap in two eyes: Streptococcus intermedius and Mycobacterium abscessus. The mean visual acuity preendophthalmitis, at presentation, and at 6 months were 20/267, 20/5,944, and 20/734, respectively. The visual acuity improved 9.08 ± 11.78 Early Treatment Diabetic Retinopathy Study lines from presentation to 6 months. Six-month visual acuity was correlated with preendophthalmitis visual acuity (r = 0.92, P = 0.003) but not presenting visual acuity (P = 0.838). CONCLUSION: Visual acuity at 6 months is correlated with preendophthalmitis visual acuity, not presenting visual acuity. Endophthalmitis should be considered in the differential diagnosis of painless intraocular inflammation any time after keratoprosthesis implantation, even if Seidel negative.

Endophthalmitis After Descemet Stripping Endothelial Keratoplasty: Microbiological Yield and Visual Outcomes.

PURPOSE: To describe the clinical presentation, management, and visual outcomes of 6 eyes with endophthalmitis after Descemet stripping endothelial keratoplasty (DSEK). DESIGN: Retrospective case series. METHODS: Setting: Tertiary, academic eye center. StudyPopulation: Individuals developing endophthalmitis after DSEK at the Duke Eye Center from January 1, 2009, to January 1, 2018, with at least 6 months of follow-up. ObservationProcedure: Retrospective chart review. OutcomeMeasures: Diagnostic procedures, microbiological yield, and visual outcomes. RESULTS: Six eyes of 6 patients were identified. Mean time from surgery to presentation was 51 days (range, 4-137 days). Dense vitreous opacities were present in all cases. Five of 6 cases (83%) had culture-proven infectious endophthalmitis (2 Candida glabrata, 2 coagulase-negative Staphylococcus, 1 Streptococcus pneumoniae). Aqueous tap yielded positive culture in 2 of 2 cases with adequate sample (100%); needle vitreous tap yielded positive culture in 0 of 3 cases. One eye underwent vitrectomy on presentation, and 3 eyes (50%) underwent subsequent vitrectomy for persistent endophthalmitis after a mean of 37 days. Mean pre-endophthalmitis visual acuity (VA) was 20/64; mean VA at 6 months was 20/2069 (average 15 ETDRS lines lost). VA at 6 months was light perception or no light perception in 3 of 6 cases (50%). One eye underwent enucleation at 6 months, and 1 eye became phthisical 1 year after endophthalmitis. CONCLUSIONS: DSEK-related endophthalmitis may lead to severe vision loss, even with prompt and appropriate treatment. Aqueous tap had a higher culture yield than needle vitreous tap in our series.

Hydrogel ocular sealant for clear corneal incisions in cataract surgery.

PURPOSE: To assess the relationship between use of a hydrogel ocular sealant (Resure) to secure clear corneal incisions (CCIs) in cataract surgery and surgeon efficiency, patient symptomatology, and postoperative results. SETTING: Duke University Eye Center, Durham, North Carolina, USA. DESIGN: Retrospective case series. METHODS: A 1:1 matched cohort of hydrogel sealant exposure-discordant eyes of cataract surgery patients was retrospectively generated. Consecutive patients who had bilateral cataract surgery during the study period and in whom the hydrogel sealant was used to secure the CCI in only 1 of the 2 eyes were included in the study. The relationship between use of the hydrogel sealant and surgical time, 1-day postoperative foreign-body sensation, clinically noted corneal edema, and intraocular pressure (IOP) was evaluated. RESULTS: Ninety eyes of 45 patients were included in the study. One day postoperatively, no wound leak was found in any eye; the sealant was noted to be out of place in 2 (4.4%) of 45 cases. No statistically significant difference was found between sealant and non-sealant eyes in total surgical time (P = .16) or in IOP (P = .55), corneal edema (P = 1.00), or foreign-body sensation (P = .38) 1 day postoperatively. CONCLUSION: The hydrogel sealant was not observed to affect duration of surgery or 1-day postoperative IOP, corneal edema, or foreign-body sensation.

Clinical Implications of Direct Immunofluorescence Findings in Patients With Ocular Mucous Membrane Pemphigoid.

PURPOSE: To examine the clinical implications of positive or negative direct immunofluorescence biopsies (DIF) in patients with clinically typical ocular mucous membrane pemphigoid (MMP). DESIGN: Retrospective cohort study. METHODS: The study population was patients with clinically typical ocular MMP disease with documented DIF results who were followed for at least 1 year at the Duke University multidisciplinary ocular MMP clinic. Data were collected by chart review and included patient demographics, clinical examination findings, and history of autoimmune disease and/or malignancy, as well as topical, systemic, and surgical treatments received. Main outcome measures included MMP Disease Area Index, Foster stages, proportion legally blind, duration of follow-up, and use of systemic immunosuppression and ocular procedures in treatment. RESULTS: In multivariable analysis restricted to 55 patients, patients with negative and positive biopsies were similar in the outcome measures; however, positive-biopsy patients were more likely to be treated with systemic immunosuppression and were followed for longer at our clinic. Patients with isolated ocular disease were also more likely to have negative biopsies compared to those who also had extraocular disease. Patients who had conjunctival biopsies were more likely to have a negative direct immunofluorescence result than patients with biopsies from other sites. CONCLUSIONS: We encourage clinicians and patients to consider treatment with systemic immunosuppression even in the absence of diagnosis confirmation by DIF. Furthermore, this study supports current standard of care to pursue a nonocular biopsy of normal-appearing, perilesional skin or oral mucosa when possible.

Ocular Surface Epithelial Atypia Mimicking Squamous Neoplasia in Association With Ulcerative Colitis.

PURPOSE: Inflammatory bowel disease may be associated with extraintestinal manifestations. We report a case of severe reactive epithelial atypia resembling ocular surface squamous neoplasia (OSSN) in a patient with ulcerative colitis (UC). METHODS: Case report. RESULTS: A 32-year-old woman presented with sequential, progressive keratoconjunctival lesions in the left and right eyes, and both lesions were excised. Anterior segment optical coherence tomography demonstrated features similar to OSSN, whereas histological examination revealed severe reactive epithelial atypia mimicking severe dysplasia. Shortly after treatment of the second eye, the patient was diagnosed with UC. Residual disease improved dramatically in response to systemic corticosteroids. CONCLUSIONS: Severe ocular surface epithelial atypia resembling OSSN may be seen in association with UC.

Keratomalacia in a Patient With Psychogenic Vitamin A Deficiency.

PURPOSE: To report the clinical and histopathological findings of a patient with bilateral keratomalacia arising from severe vitamin A deficiency from panic disorder-related malnutrition. METHODS: Case report. RESULTS: A 47-year-old male with panic disorder presented with 1 month of painful vision loss sequentially affecting the right and left eyes. He exhibited bilateral conjunctival xerosis with complete corneal melt in the right eye and a large corneal epithelial defect with underlying anterior chamber inflammation in the left eye. Laboratory investigation revealed undetectable serum vitamin A levels attributed to self-induced vomiting and starvation. He was treated with high-dose vitamin A, but the right eye required enucleation. The histological findings are reported. CONCLUSIONS: Vitamin A deficiency in the absence of organic gastrointestinal abnormalities is exceedingly rare in the developed world. A strong index of suspicion and thorough review of systems are invaluable in evaluating patients with unexplained corneal melt.

Atypical Fibroxanthoma of the Bulbar Conjunctiva.

PURPOSE: To report a rare case of atypical fibroxanthoma (AFX) of the bulbar conjunctiva, and to compare it with previously published cases of conjunctival AFX. METHODS: A 37-year-old woman developed a growth on the bulbar conjunctiva of her left eye that increased in size and redness over 4 months and was associated with blurry vision in the left eye, occasional diplopia, irritation of the eye, and increasing tearing. The mass was surgically excised. RESULTS: Slit-lamp examination disclosed a highly vascularized conjunctival lesion with intact lustrous epithelium and a raised nodular edge encroaching on the nasal corneal limbus of the left eye. Pathological examination and immunohistochemistry were diagnostic of AFX. CONCLUSIONS: AFX of the conjunctiva is rare, with this being only the fifth example of this neoplasm reported at this site. Complete surgical excision is the most appropriate treatment option.