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.

Lessons Learned From Ocular Graft versus Host Disease: An Ocular Surface Inflammatory Disease of Known Time of Onset.

ABSTRACT: The ocular surface inflammatory disorders (OSIDs) comprise a group of conditions characterized by persistent inflammation of the ocular surface and adnexal tissues. Systemic autoimmune diseases and hypersensitivity reactions cause them, and, if left untreated, can result in severe inflammatory dry eye, corneal damage, and vision loss. Ocular graft-versus-host disease (oGVHD) forms part of the ocular surface inflammatory disease umbrella. It is a condition occurring after allogeneic hematopoietic stem cell or bone marrow transplantation, usually in chronic graft-versus-host disease. oGVHD can virtually affect any ocular adnexal tissue, especially the meibomian glands, and cause persistent inflammation, tissue fibrosis, and subsequent chronic, severe dry eye disease. Among the OSIDs, oGVHD has the particularity that it has a "time zero," meaning we know when the disease started. As such, preclinical models have leveraged this to investigate the molecular mechanisms involved in the damage oGVHD causes to the ocular surface. In oGVHD, establishing a "time zero" allows for predicting the clinical course and establishing adequate treatment. This is also possible because the inflammatory infiltration occurs in ocular surface tissues, which are readily accessible. Using oGVHD, we might be able to understand the immune response mechanisms in other OSIDs better (i.e., Sjögren syndrome, Stevens-Johnson syndrome, among others). This review presents an up-to-date overview of the pathogenesis, clinical presentation, and treatment of oGVHD. In addition, we will discuss the value of the "time zero" concept in the study of oGVHD.

Outcomes of accelerated corneal cross-linking for pediatric and adult keratoconus: a comparative study.

PURPOSE: To compare the visual, refractive, and topographic outcomes of a high irradiance accelerated corneal crosslinking (ACXL) protocol after a 12-month follow-up between pediatric and adult patients with progressive keratoconus (KC). METHODS: Retrospective, comparative, cohort study. Patients with KC were divided into two groups: pediatric (≤ 18 years) and adult (> 18 years). All of them were managed with epi-OFF ACXL (30 mW/cm2, 8 min, pulsed 1:1 on and off = 7.2 J/cm2). Visual, refractive, and topographic values were measured preoperatively and at 1, 3, 6, and 12 months postoperative. KC progression, defined as a Kmax increase of ≥ 1D during follow-up, was recorded. RESULTS: Eighty-nine eyes (53 patients) were included for analysis; 45 (50.6%) eyes were from pediatric patients and 44 (49.4%) from adults. At one-year follow-up, pediatric patients experienced significantly higher rates of progression (22.2% vs. 4.5%, p = .014). Contrariwise, female gender (Beta = - 3.62, p = .018), a baseline uncorrected visual acuity of Snellen ≥ 20/60 (Beta = - 5.96, p = .007), and being ≥ 15 years at ACXL treatment (Beta = - 0.31, p = .021) were associated with non-progressive disease. A significant improvement in best-corrected visual acuity, Kmin, Km, and Kmax was recorded in both groups. Overall, 86.5% of eyes from both groups showed Kmax stabilization or improvement. CONCLUSIONS: Despite the similarity in visual, refractive, and topographic outcomes in both groups, younger age was associated with KC progression after ACXL at one year of follow-up.

Adalimumab to treat noninfectious pediatric chronic anterior uveitis: a case series.

PURPOSE: Evaluate the response to adalimumab (ADA) in pediatric chronic anterior uveitis (pCAU). METHODS: Retrospective chart review of pCAU patients treated with ADA. Outcomes evaluated included the proportion of patients achieving zero ocular inflammation and discontinuation of topical corticosteroids, visual outcomes, and incidence of uveitis recurrences after ≥ 12 months of prescribing ADA. Incidence and risk factors for developing anti-adalimumab antibodies (AAAs) were also evaluated. RESULTS: Of 27 children aged 11 years, 16 (59%) were Caucasian and 6 (22%) African Americans. Thirteen (48%) patients had idiopathic pCAU, 12 (44%) had juvenile idiopathic arthritis (JIA) related pCAU, and 2 (7%) had tubulointerstitial nephritis and uveitis syndrome. At baseline, African American children had worse visual acuity (p = 0.026). At 1 year, 21 (78%) children achieved zero ocular inflammation (remission). Risk factors associated with non-remission were being African American (20% vs. 94%, p = 0.003) and experiencing ≥ 1 episode of uveitis recurrence (100% vs. 0%, p < 0.001). Six episodes of uveitis recurrence were documented in five children, four of whom were African American. Topical corticosteroids were discontinued in 83% of children, and visual acuity remained stable for 1 year. Twelve children were tested for AAAs due to arthritis or uveitis flare-ups, with five (42%) being positive. No significant factors were associated with the development of AAAs. CONCLUSIONS: We found that ADA is effective in controlling inflammation, reducing the need for topical corticosteroids, and maintaining visual acuity in pCAU. There appears to be racial differences in African American children who had worse baseline disease and poorer outcomes. Studies are necessary to understand better and address these disparities.

Congenital Orbital Glial Heterotopia Associated with Clinicopathological Anophthalmia: A Case Report.

Glial heterotopia (GH) is the presence of glial tissue outside the cranial cavity, without communication with the brain. The orbital location usually presents as eyelid swelling, strabismus, and proptosis. This is considered a congenital location that usually presents at birth. Its association with anophthalmia is uncommon. We report the case of a 2-day-old male neonate with left congenital intraorbital lesion presenting with massive proptosis. No eyeball could be seen. Preoperative magnetic resonance imaging disclosed a large and predominantly cystic mass occupying and protruding from the left orbit without intracranial extension. In the operating theatre, a large amount of fluid was aspirated prior to total resection of the mass. Chemical analysis of the fluid was compatible with cerebrospinal fluid. Histologically, the tumor was composed of mature neuroglial tissue and ependymal cells. Despite multiple sections, no choroid plexus or intraocular content was found. The diagnosis of GH with anophthalmia was made.

Selective laser trabeculoplasty is safe and effective in patients previously treated with prostaglandin analogs: An evidence-based review.

PURPOSE: Prostaglandin analogs (PGAs) are first-line treatments for ocular hypertension (OHT) and open-angle glaucoma (OAG). However, frequent side effects and high costs hinder patient's compliance resulting in disease progression. Evidence suggests selective laser trabeculoplasty (SLT) may be considered a first-line treatment for OHT and OAG due to its safety profile, minor side effects, and reduced costs. Considering that PGAs and SLT share action mechanisms, it is hypothesized that previous PGA therapy may affect subsequent SLT efficacy. Therefore, we analyzed if PGAs reduce SLT efficacy. METHODS: An evidence-based review was performed to assess the safety and efficacy of SLT in patients previously treated with PGAs. For this purpose, we performed an extensive literature search using the National Library of Medicine's PubMed and Google Scholar database for all English language articles published until May 2021. RESULTS: There is evidence of non-superiority of PGAs therapy versus SLT for OHT and OAG. A multicenter, randomized, observer-masked clinical trial (RCT) of untreated OHT and OAG patients concluded that SLT should be offered as the first-line treatment for these patients. This study was supported by a meta-analysis of RCTs, comparing SLT efficacy versus antiglaucoma drugs only, with the advantage of an SLT lower rate of adverse effects. CONCLUSIONS: Cost-effectiveness, patient compliance, and antiglaucoma drugs' side effects, including higher surgical failure, favor consideration of SLT as first-line therapy for OAG and OHT. Furthermore, SLT efficacy does not seem to be affected by prior PGA administration; however, larger cohort, comparative, multicenter RCTs are necessary to answer this question.

Polymyositis and dermatomyositis: ocular manifestations and potential sight-threatening complications.

Dermatomyositis (DM) and polymyositis (PM) are idiopathic inflammatory myopathies characterized by progressive, symmetric, mainly proximal muscle weakness. DM is also characterized by cutaneous involvement. However, other clinical features, systemic involvement, histopathological findings, response to treatment, and prognosis, differ significantly. Although uncommon, ocular manifestations in DM and PM may potentially affect any structure within the eye. Notwithstanding being generally mild, ocular involvement in DM and PM may result in significant morbidity. Left untreated, significant retinal inflammation associated with hemorrhage and detachment may occur, leading to significant vision loss. This review aims to present an up-to-date overview for rheumatologists about the ocular involvement and potential complications of DM and PM and when to refer to the ophthalmologist to avoid sight-threatening complications.

Coats Disease in 9 Patients: A Hispanic Case Series.

BACKGROUND/AIM: To describe demographic and clinical characteristics, treatment, and visual prognosis of Coats disease in Hispanic patients. METHODS: A retrospective chart review was performed on nine patients (ten eyes) diagnosed with Coats disease in our two clinical centrers from 2004 - 2017. RESULTS: Mean age at diagnosis was 5.5 years (range 1 - 12 years) and mean follow-up time was 48 months (range 9 - 108 months). Eight patients (89%) were male and had unilateral disease and one (11%) female patient had bilateral disease. In 40% of the cases, patients were asymptomatic. Visual acuity at first presentation was worse than hand motion in 60% of the eyes. Half of the eyes (5/10 eyes, 50%) had exudative retinal detachment (≥ stage IIIA). Vascular ablation with cryotherapy combined with retinal photocoagulation was the most frequent therapeutic approach (40%). Despite anatomical success at 6 months in 100% of the treated eyes, visual outcome at 1 year of treatment was poor (worse than 20/200) in 70% of the cases. CONCLUSIONS: In our case series, patients were mostly asymptomatic on presentation, with severe stages of Coats disease. Even with anatomical success after surgical treatment in all treated cases, long-term visual prognosis remained very limited.

Reproducibility, Repeatability, and Correlation of Central Corneal Thickness Measurement with the Pentacam Scheimpflug System and Ultrasound Pachymetry.

BACKGROUND/AIM: The importance of an accurate determination of central corneal thickness (CCT) relies on its diagnostic and therapeutic implications in glaucoma, corneal ectasias, corneal edema and endothelial function monitoring, and refractive surgery suitability, among others. We aimed to analyze the repeatability, reproducibility, correlation, and laterality variations of CCT measurements performed with the Pentacam HR and the standard of care ultrasound A-scan (USP). METHODS: A cross-sectional study including CCT measurements of healthy individuals was performed by three independent examiners with the Pentacam HR and USP. Intra-observer and inter-observer variations were calculated with intra-class correlation coefficients (ICCs). Bland-Altman plots and 95% limits of agreement (95% LoA) were used to assess the agreement between devices. Linear correlation was calculated with Pearson's coefficient. RESULTS: Thirty individuals (60 eyes), including 10 (33.3%) men and 20 (66.6%) women, with a mean age of 30.0 ± 9.1 years, were studied. No statistical differences were found in CCT measurements between Pentacam HR (range 500 - 609 µm) and USP (range 498 - 628 µm). There was a high degree of correlation in repeatability and reproducibility of each independent device (ICC > 0.90). Pearson's correlation between 1 vs. 2, 2 vs. 3, and 3 vs. 1 Pentacam HR attempts were 0.914, 0.958, and 0.925, respectively (p < 0.001). Corresponding results for USP were 0.957, 0.957, and 0.943 (p < 0.001). The Pentacam HR tended to overestimate CCT by a mean difference of 3.77 µm (95% LoA, - 24.9 - 18.4). Right eyes were also overestimated (- 3.6 ± 14.1 µm) with the Pentacam HR device, whereas left eyes were underestimated (1.3 ± 11.1 µm). CONCLUSIONS: The Pentacam HR device provides reliable operator-independent estimates of CCT. Right eyes exhibited a tendency to overestimate with the Pentacam HR. We suspect this difference is due to USP underestimation related to patients' position while performing the study. In clinically relevant scenarios, performing a third measurement and cautiously measuring right eyes can provide higher accuracy.

Demographic profile and clinical course of Fuchs endothelial corneal dystrophy in Mexican patients.

PURPOSE: To describe the demographic characteristics and clinical course of Fuchs endothelial corneal dystrophy (FECD) in a Mexican-mestizo population. METHODS: A retrospective observational and longitudinal study was performed in consecutive patients with the clinical diagnosis of Fuchs endothelial corneal dystrophy seen at our institution. Initial and last follow-up best-corrected visual acuity, slit-lamp findings, and specular microscopy endothelial morphometric parameters were analyzed. RESULTS: One hundred and two eyes belonging to 51 patients were included in the analysis. Median age at the time of diagnosis was 69 years (range, 25-87 years) with a female-to-male ratio of 3.3:1. Visual loss (40%) followed by glare (13.3%) and fluctuating matutine vision loss (13.3%) was the most common complaints at presentation. Regarding FECD staging, 65 (63.7%) were classified as stage-I FECD, 21 (20.6%) stage-II, and 15 (14.7%) as stage-III. A high percentage of eyes (44.1%) presented visual impairment ( ≤ 20/50) at presentation, and the presence of isolated corneal guttata was the most common stage of presentation (64%) at slit-lamp examination. While fifty-nine (57.8%) eyes did not require any medical or surgical management, 17 (16.7%) eyes were managed with hypertonic saline eyedrops alone or in combination with bandage contact lens, and 18 (17.6%) required corneal transplantation. Penetrating keratoplasty alone (8 eyes, 44.4%), or in combination with cataract extraction and intraocular lens implantation (3 eyes, 16.7%), was the most frequent surgical technique performed. CONCLUSION: Demographical characteristics of Fuchs dystrophy regarding age at presentation, gender distribution, and clinical stage at the time of diagnosis did not differ significantly from other international reports. Almost 20% of these patients will require keratoplasty during the disease, emphasizing the need for safer and more reproducible keratoplasty techniques.

Clinical profile of melanocytic lesions of the ocular surface in a Hispanic population.

PURPOSE: To determine the prevalence, clinical characteristics, and demographic factors of melanocytic lesions of the ocular surface, such as racial melanosis, primarily acquired melanosis, conjunctival nevus, and conjunctival melanoma in a Hispanic population. MATERIALS AND METHODS: A cross-sectional and observational study was undertaken in a tertiary referral ophthalmological center in northern Mexico from December 2020 to April 2021. All patients attending an ophthalmology specialty clinic were screened during their first visit in order to detect melanocytic lesions of the ocular surface. Demographic factors, clinical characteristics, and diagnosis and treatment were recorded. RESULTS: 227 patients were screened for melanocytic lesions. Melanocytic lesions were identified in 114 patients (50.2%). The prevalence of the different melanocytic lesions in the screened population was racial melanosis, 45.3%; primary acquired melanosis, 3.5%, and conjunctival nevus 1.3%. No conjunctival melanoma was identified in the screened population. Primary acquired melanosis was more common in the fifth to sixth decade of life and in females. Racial melanosis showed no gender predilection and was also more common in the fifth to sixth decade of life. Only 1 melanocytic lesion (a primary acquired melanosis) required medical treatment with excisional biopsy and cryotherapy. CONCLUSION: The prevalence of racial melanosis is remarkably high in the Hispanic population. While less prevalent, primary acquired melanosis is also present in a considerable percentage of Hispanic patients. Both melanocytic lesions exhibit demographic characteristics that match those previously reported in the medical literature.

High prevalence of angle-closure glaucoma in Vogt-Koyanagi-Harada disease.

PURPOSE: To determine the prevalence, clinical characteristics, and mechanisms of secondary glaucoma in Vogt-Koyanagi-Harada (VKH) disease. METHODS: This retrospective, longitudinal observational study analyzed the demographic data, disease stage, glaucoma development, intraocular pressure, best-corrected visual acuity, lens status, optic nerve, gonioscopy, management, and visual outcomes of VKH disease. Clinical features were used to categorize the stage of VKH disease. VKH eyes were divided into two groups, with or without glaucoma, undergoing further analysis, including statistical analysis. RESULTS: 305 eyes of 155 patients with VKH disease with a median follow-up of 22 months were included. Secondary glaucoma developed in 67 (22%) eyes, most of which (64.2%) had chronic recurrent VKH at presentation. Angle-closure was present in 55 (82.1%) of glaucoma eyes. Peripheral anterior and posterior synechiae were present in 58 (86.6%) and 51 (76.1%) eyes, respectively. Pupillary block and posterior synechiae resulted in iris bombé in 17 (25.4%) eyes with glaucoma. At the last visit, visual acuity was worse in eyes with glaucoma (p < 0.001). CONCLUSION: We found that angle-closure disease is a significant cause of secondary glaucoma in VKH. Eyes with glaucoma were more likely to present in the chronic recurrent stage of the disease.

Ocular involvement and complications of lichen planus, lichen planus pigmentosus, and lichen planopilaris: A comprehensive review.

Ocular involvement of lichenoid dermatoses, such as lichen planus (LP), lichen planus pigmentosus (LPP), and lichen planopilaris (LPL), although uncommon, is associated with skin manifestations. Isolated ocular involvement is very rare. When lesions are confined to the skin, the dermatologist inquires and evaluates for oral and genital symptoms and lesions, respectively; hence, eye manifestations are commonly neglected by the non-ophthalmologist. Ocular involvement in LP, LPP, and LPL may result in significant morbidity. An ophthalmic interrogatory and a gross ophthalmic evaluation performed by the dermatologist may unravel ocular signs and symptoms that require evaluation by an eye specialist. Ocular surface inflammation and scarring, when untreated, results in serious complications such as corneal perforation and permanent vision loss. This review aims to present an up-to-date overview for the dermatologist of the ocular involvement and complications of LP, LPP, and LPL, and when to refer to the ophthalmologist to prevent blinding complications.

Isotretinoin and the eye: A review for the dermatologist.

Due to the prevalence of acne vulgaris, isotretinoin is one of the most prescribed drugs among physicians and dermatologists. Although exhibiting an adequate safety profile, adverse events secondary to isotretinoin use are common. Before prescribing isotretinoin, physicians usually inquire about pregnancy and perform serologic tests including cholesterol, triglycerides, and liver enzymes. Ocular manifestations are commonly neglected. Despite being generally mild, ocular manifestations related to either topical or systemic isotretinoin may cause important ocular morbidity. The ocular surface is the most affected site within the eye; however, retinal and optic nerve disease also have been documented. Evaporative dry eye disease, which may range from mild to severe, is the most common adverse ocular effect associated with isotretinoin use. The aim of this review is to present an up-to-date overview for the dermatologist about the prevention, diagnosis, and treatment of the ocular side effects of isotretinoin, and when to refer to the eye specialist.

The Yin and Yang of non-immune and immune responses in meibomian gland dysfunction.

Meibomian gland dysfunction (MGD) is a leading cause of dry eye disease and one of the most common ophthalmic conditions encountered in eye clinics worldwide. These holocrine glands are situated in the eyelid, where they produce specialized lipids, or meibum, needed to lubricate the eye surface and slow tear film evaporation - functions which are critical to preserving high-resolution vision. MGD results in tear instability, rapid tear evaporation, changes in local microflora, and dry eye disease, amongst other pathological entities. While studies identifying the mechanisms of MGD have generally focused on gland obstruction, we now know that age is a major risk factor for MGD that is associated with abnormal cell differentiation and renewal. It is also now appreciated that immune-inflammatory disorders, such as certain autoimmune diseases and atopy, may trigger MGD, as demonstrated through a T cell-driven neutrophil response. Here, we independently discuss the underlying roles of gland and immune related factors in MGD, as well as the integration of these two distinct mechanisms into a unified perspective that may aid future studies. From this unique standpoint, we propose a revised model in which glandular dysfunction and immunopathogenic pathways are not primary versus secondary contributors in MGD, but are fluid, interactive, and dynamic, which we likened to the Yin and Yang of MGD.

Leukemic infiltration of the ciliary body in a child with T-cell acute lymphoblastic leukemia.

A 14-year-old boy presented after 2 months of vision loss, redness, and pain in the right eye, initially treated as anterior uveitis with topical corticosteroids. He had a 1-year history of T-cell acute lymphoblastic leukemia, which had been in remission for 6 months. On examination, visual acuity in the right eye was light perception, with 4+ anterior chamber cells, pupillary membrane, and an intumescent cataract. Ultrasound biomicroscopy (UBM) revealed a ciliary body mass and capsular bag rupture. After consultation with his oncologist, he received 10 radiotherapy sessions. At 1 month, UBM showed resolution of the mass. After 1 year of remission, the patient underwent pars plana vitrectomy, pupillary membranectomy, and placement of a scleral-fixated intraocular lens. Thirty months after surgery, visual acuity was 20/25. Leukemic infiltration of the ciliary body is a rare manifestation of the disease that is often misdiagnosed as uveitis.