Clinical Course and Outcomes of Autoimmune Versus Non-Autoimmune Surgically Induced Scleral Necrosis: A Multicentric Comparative Study.

BACKGROUND: To analyze the clinical course and outcomes of autoimmune vs. non-autoimmune surgically induced scleral necrosis (SISN). METHODS: Multicentric, retrospective, comparative cohort study. Eighty-two eyes of 70 patients with SISN were classified according to pathogenic mechanism into autoimmune vs. non-autoimmune. Main outcome measures included necrosis onset, type of surgery, associated systemic disease, visual acuity, and treatment were analysed in patients followed for ≥ 6 months. RESULTS: Forty-six (65.7%) patients were women, and the median age was 66 (range: 24-90) years. Most patients (82.9%) had unilateral disease. The median time between surgery and SISN onset was 58 (1-480) months. Thirty-one (37.8%) eyes were classified as autoimmune, and 51 (62.2%) as non-autoimmune SISN. Autoimmune SISN was associated with a shorter time between the surgical procedure and SISN onset than non-autoimmune cases (median of 26 vs. 60 months, p = 0.024). Also, autoimmune SISN was associated with cataract extraction (93.5% vs. 25.5%, p < 0.001), severe scleral inflammation (58.1% vs. 17.6%, p < 0.001), and higher incidence of ocular complications (67.7% vs. 33.3%, p = 0.002) than non-autoimmune cases. Remission was achieved with medical management alone in 44 (86.3%) eyes from the non-autoimmune and in 27 (87.1%) from the autoimmune group (p = 0.916). Surgical management was required in 11 (13.4%) eyes, including two requiring enucleations due to scleral perforation and phthisis bulbi. CONCLUSIONS: Eyes with autoimmune SISN had a higher rate of cataract surgery, severe scleral inflammation, and ocular complications. Early SISN diagnosis and appropriate management, based on clinical features and pathogenic mechanisms, are critical to avoid sight-threatening complications.

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.

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.

Delayed presentation of surgically induced scleral necrosis after I-BRITE procedure treated with immunosuppressive therapy.

Surgically induced scleral necrosis (SISN) is an uncommon complication of ocular procedures. Cosmetic eye-whitening surgery involves conjunctival and Tenon's capsule dissection, cautery, and mitomycin C application. We report the case of a 36-year-old white woman referred to our clinic for severe pain, scleral inflammation, and necrosis in both eyes 9 years after I-BRITE, an elective eye-whitening procedure. An extensive workup yielded negative results. The patient improved with aggressive lubrication and topical and high-dose systemic prednisone (60 mg), with recurrence upon steroid tapering. Concomitant weekly methotrexate was added, resulting in inflammatory control and allowing discontinuance of topical and oral steroids.

Ocular surface disease: a known yet overlooked side effect of topical glaucoma therapy.

Ocular surface disease (OSD), a disorder affecting the lacrimal and meibomian glands and the corneal and conjunctival epithelium, is a well-known complication of topical glaucoma therapy. OSD can present as a new or pre-existing condition that virtually any anti-glaucoma formulation can exacerbate. As such, both glaucoma and OSD frequently coexist. Typical OSD symptoms include ocular discomfort, redness, burning, and dryness, whereas signs include periorbital and eyelid skin pigmentation, conjunctival scarring, and superficial punctate keratitis. Pressure-lowering eyedrops can cause toxic, allergic, and inflammatory reactions on the ocular surface. The latter can result from either preservatives or direct toxicity from the active molecule. Although usually mild, OSD can cause significant symptoms that lead to poor quality of life, decreased compliance to therapy, glaucoma progression, and worse visual outcomes. Given the chronic nature of glaucoma, lack of curative therapy, and subsequent lifelong treatment, addressing OSD is necessary. This manuscript aims to provide an up-to-date overview of OSD's signs, symptoms, and pathogenic mechanisms from glaucoma therapy toxicity.

Wessely corneal ring phenomenon: An unsolved pathophysiological dilemma.

The cornea is a densely innervated avascular tissue showing exceptional inflammatory and immune responses. The cornea is a site of lymphangiogenic and angiogenic privilege devoid of blood and lymphatic vessels that limits the entry of inflammatory cells from the adjacent and highly immunoreactive conjunctiva. Immunological and anatomical differences between the central and peripheral cornea are also necessary to sustain passive immune privilege. The lower density of antigen-presenting cells in the central cornea and the 5:1 peripheral-to-central corneal ratio of C1 are two main features conferring passive immune privilege. C1 activates the complement system by antigen-antibody complexes more effectively in the peripheral cornea and, thus, protects the central corneas' transparency from immune-driven and inflammatory reactions. Wessely rings, also known as corneal immune rings, are noninfectious ring-shaped stromal infiltrates usually formed in the peripheral cornea. They result from a hypersensitivity reaction to foreign antigens, including those of microorganism origin. Thus, they are thought to be composed of inflammatory cells and antigen-antibody complexes. Corneal immune rings have been associated with various infectious and noninfectious causes, including foreign bodies, contact lens wear, refractive procedures, and drugs. We describe the anatomical and immunologic basis underlying Wessely ring formation, its causes, clinical presentation, and management.

Noxious effects of riot control agents on the ocular surface: Pathogenic mechanisms and management.

Riot Control Agents (RCAs) are chemical compounds used by law enforcement agencies to quell violent demonstrations as an alternative to lethal force and as part of police/military training. They are also known as tear gases because of the hallmark ocular irritation and lacrimation they cause. The most common RCAs include oleoresin capsicum (contained in Mace and pepper spray), chlorobenzylidene malononitrile, dibenzoxazepine, and chloroacetophenone (previously the main content of Mace); some of which have been in use for decades. Their immediate incapacitating effects are mediated through polymodal afferent fibers innervating the corneal surface, inducing the release of peptides that cause neurogenic inflammation. Although previously thought to have only transient effects on exposed patients more severe complications such as corneal stromal opacities, corneal neovascularization, neurotrophic keratopathy, conjunctival necrosis, and pseudopterygium can occur. Concerningly, the lack of research and specific therapies restrict the current management to decontamination and symptom-tailored support. This manuscript will provide an overview of the toxic mechanisms of RCAs, their clinical manifestations, and current therapy after exposure to tear gases.

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.

Risk factors for secondary Glaucoma in patients with Vogt-Koyanagi-Harada disease.

BACKGROUND/PURPOSE: Identify the prevalence and risk factors for secondary glaucoma among Mexican-mestizo patients with Vogt-Koyanagi-Harada Disease (VKH). METHODS: Retrospective cohort study analyzing the demographic, clinical, and epidemiological variables. Risk estimates were calculated using a Cox proportional hazards regression model. RESULTS: One hundred eyes of 50 patients, 44 (88%) women and 6 men (12%) with a median age of 35.5 years (IQR 29-46) and a median follow-up time of 72 months (IQR 13.7-126.7) were analyzed. The prevalence of glaucoma was 20%, with angle-closure accounting for 70% of all cases. Significant clinical risk factors for glaucoma development were a chronic recurrent stage at presentation (RR 2.88, 95% CI 1.11-12.63, p = 0.037), ≥ 2 episodes of recurrent anterior uveitis (RR 8.52, 95% CI 2.02-35.92, p < 0.001), angle-closure disease (ACD, RR 7.08, 95% CI 2.44-20.48, p < 0.001), iris bombé (RR 5.0, 95% CI 2.10-11.90, p < 0.001), and peripapillary atrophy (RR 3.56, 95% CI 1.43-8.85, p < 0.001). Exposure to > 24 months of oral (RR 9.33, 95% CI 2.21-39.28, p < 0.001) or > 12 months of topical corticosteroids (RR 3.88, 95% CI 1.31-11.46, p = 0.007) were associated with an increased likelihood for secondary glaucoma development. CONCLUSION: Glaucoma is a frequent complication of VKH, often attributed to mixed pathogenic mechanisms. Chronic disease at presentation, recurrent inflammation, angle-closure mechanisms, iris bombé, and peripapillary atrophy represent clinically significant risk factors for developing secondary glaucoma. Prompt and aggressive steroid-spearing immunosuppressive therapy for adequate inflammation control may lower the risk of glaucoma in VKH.

Burden and depression among informal caregivers of visually impaired patients in Mexico.

BACKGROUND: The needs of informal caregivers who provide care to family relatives with visual impairment are often neglected, resulting in burden and depression. OBJECTIVE: To determine the degree of burden and the prevalence of major depression experienced by caregivers, defined as non-paid family relatives, of legally blind individuals in a Mexican population. METHODS: Observational, single-center, cross-sectional study in adults providing care to their family relatives with visual impairment (visual acuity ≤ 20/200 in the best eye for at least 3 months). According to visual impairment degree, care provided included activities of daily living (ADL) and instrumental ADL. Burden of care was evaluated with the Zarit burden interview (ZBI)-22 and the prevalence of major depression was determined by the patient health questionnaire (PHQ)-9. RESULTS: 115 patients and 115 caregivers were included. Male caregivers had significantly higher ZBI-22 (28.7 ± 15.5 vs. 19.2 ± 12.6, p = 0.001) and PHQ-9 (10.0 ± 5.5 vs. 5.3 ± 5.1, p < 0.001) scores than females. Likewise, parent caregivers of adult children and the hours of daily care were significantly associated with higher burden and depression scores. A significant linear correlation between ZBI-22 and PHQ-9 scores in caregivers was also found (r = 0.649, p < 0.001). CONCLUSIONS: Male caregivers, parent caregivers of adult children, and caregivers providing greater hours of care were at higher risk of burden and depression. Upon diagnosis of visual impairment, adults providing care to visually impaired family relatives should be screened for burden and depression and referred to a mental health specialist when necessary. Tailored interventions targeting the caregivers' needs are required to reduce burden and depression.