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.

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.

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.

Rheumatoid arthritis-associated peripheral ulcerative keratitis outcomes after early immunosuppressive therapy.

BACKGROUND/AIMS: To evaluate the role of early immunosuppressive therapy (IMT) in the management of rheumatoid arthritis (RA)-associated peripheral ulcerative keratitis (PUK). METHODS: Single-centre, retrospective, comparative cohort study. Patients with RA-associated PUK were divided into two groups; those exposed to and those not exposed to early IMT, defined as administrating therapy within the first 4 weeks from the PUK onset. Outcomes included PUK recurrence, control of inflammation and development of ocular complications, including corneal scarring and perforation, cataract formation or progression and permanent visual loss. RESULTS: A total of 52 eyes from 36 patients were included for analysis; 37 (71.2%) eyes received early IMT and 15 (28.8%) eyes did not. Follow-up time was 41.2+53.3 months (range: 4-236 months). While early IMT was a protective factor (HR 0.345, 95% CI 0.126 to 0.946, p=0.039), late RA diagnosis after PUK onset (HR 4.93, 95% CI 1.75 to 13.85, p=0.002) and retarded (≥2 months) control of inflammation (HR 8.37, 95% CI 1.88 to 37.16, p=0.005) were risk factors for PUK recurrence. Late IMT (OR 7.75, 95% CI 2.00 to 29.99, p=0.003), an unknown diagnosis of RA at first visit (OR 4.14, 95% CI 1.15 to 14.91, p=0.030) and at least one PUK recurrence (OR 6.42, 95% CI 1.71 to 24.07, p=0.006) were risk factors for visual loss. Survival analysis rendered eyes exposed to early IMT a lower risk of PUK recurrence (p=0.039). CONCLUSION: Eyes with RA-associated PUK exposed to early IMT were more likely to achieve earlier inflammatory control, fewer recurrences and had better visual outcomes.

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.

A Practical Approach to Severity Classification and Treatment of Dry Eye Disease: A Proposal from the Mexican Dry Eye Disease Expert Panel.

Dry eye disease (DED) has a higher prevalence than many important systemic disorders like cardiovascular disease and diabetes mellitus, representing a significant quality of life burden for the affected patients. It is a common reason for consultation in general eye clinics worldwide. Nowadays, the diagnostic and therapeutic approach at the high corneal and ocular surface specialty level should be reserved for cases of severe and chronic dry eye disease associated with systemic autoimmune diseases or complicated corneal and ocular surface pathologies. In such cases, the diagnostic and therapeutic approach is often complex, elaborate, time-consuming, and costly due to the use of extensive dry eye questionnaires, noninvasive electronic diagnostic equipment, and clinical laboratory and ancillary tests. However, other eye care specialists attend a fair amount of DED cases; therefore, its diagnosis, classification, and management should be simple, practical, achievable, and effective. Considering that many patients attending non-specialized dry eye clinics would benefit from better ophthalmological attention, we decided to elaborate a practical DED classification system based on disease severity to help clinicians discriminate cases needing referral to subspecialty clinics from those they could attend. Additionally, we propose a systematic management approach and general management considerations to improve patients' therapeutic outcomes according to disease severity.

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.

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.

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.

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.

The molecular basis of neurotrophic keratopathy: Diagnostic and therapeutic implications. A review.

Neurotrophic keratopathy (NK) is a degenerative corneal disease produced by different factors, including infection, trauma, and neurogenesis, that lead to trigeminal nerve damage and impaired corneal sensitivity. Extensive epithelial breakdown, impaired corneal epithelial healing and corneal ulceration, stromal melting, and perforation are main NK features. The proliferation of the corneal epithelium is endogenously regulated by a balance between adrenergic cAMP-dependent and cholinergic cGMP-dependent pathways. A careful balance of epitheliotropic neuromediators and neurotrophic factors expressed by corneal nerves and epithelial cells, respectively, is required to maintain corneal homeostasis. Even in its early stages, NK can cause reduced vision secondary to epithelial disturbance. Diagnosing NK is challenging, requiring the acquisition of a thorough clinical history and a comprehensive neurological and ophthalmic examination. Following suspicion of a clinical NK diagnosis, corneal sensitivity must be assessed qualitatively with the wisp of the cotton-tipped applicator and quantitatively through Cochet-Bonnet esthesiometry (CBE). A myriad of therapies is used for NK, and new, more specific modalities are being developed and investigated. Medical treatment with topical recombinant human nerve growth factor and surgical treatment through corneal neurotization are promising therapies aiming to target NK pathophysiology. Coexistent ocular surface disorders must be managed concomitantly to improve its prognosis. This review describes the up-to-date knowledge of the molecular basis regarding the pathogenesis of NK, and the novel target-specific therapeutic approaches based on this molecular mechanism.

Corneal perforation associated with isolated ocular lichen planus: a case report.

INTRODUCTION: To report a case of unilateral corneal perforation due to isolated ocular lichen planus. METHODS: Interventional case report. Informed consent by the patient was obtained to publish clinical images. A 64-year-old male presented with severe vision loss and a 2-week history of corneal perforation treated with penetrating keratoplasty in the left eye. He had a longstanding diagnosis of severe chronic dry eye disease. On the initial assessment a visual acuity of 20/50 in the RE and HM perception in the left eye were documented. Biomicroscopy revealed subepithelial fibrosis on the tarsal conjunctiva and clinical signs of severe dry eye disease in both eyes. A clear corneal button and a white cataract were observed in the left eye. No other skin or mucosal lesions were observed. RESULTS: An excisional biopsy of the bulbar conjunctiva was performed under topical anesthesia. Direct immunofluorescence analysis revealed a linear deposit of fibrinogen in the basement membrane consistent with ocular lichen planus. Clinical improvement was achieved using aggressive topical lubrication, corneal epithelial regenerators, topical tacrolimus, and immunosuppressive therapy with systemic corticosteroids and cyclophosphamide. CONCLUSION: Isolated ocular lichen planus is an extremely infrequent presentation of lichen planus often indistinguishable from other cicatricial conjunctivitis. Corneal perforation is a severe complication associated with severe dry eye, not previously reported with ocular lichen planus. An adequate clinical assessment and histopathologic diagnosis are crucial to lead prompt treatment and prevent sight-threatening complications.

In Vivo Corneal Microstructural Changes in Herpetic Stromal Keratitis: A Spectral Domain Optical Coherence Tomography Analysis.

PURPOSE: To describe and analyze the microstructural changes in herpetic stromal keratitis (HSK) observed in vivo by spectral-domain ocular coherence tomography (SD-OCT) at different stages of the disease. METHODS: A prospective, cross-sectional, observational, and comparative SD-OCT analysis of corneas with active and inactive keratitis was performed, and the pathologic differences between the necrotizing and non-necrotizing forms of the disease were analyzed. RESULTS: Fifty-three corneas belonging to 43 (81.1%) women and 10 (18.8%) men with a mean age of 41.0 years were included for analysis. Twenty-four (45.3%) eyes had active keratitis, and 29 (54.7%) had inactive keratitis; the majority (83.0%) had the non-necrotizing form. Most corneas (79.1%) with active keratitis showed stromal edema and inflammatory infiltrates. Almost half of the active lesions affected the visual axis, were found at mid-stromal depth, and had a medium density. By contrast, corneas with inactive keratitis were characterized by stromal scarring (89.6%), epithelial remodeling (72.4%), and stromal thinning (68.9%). In contrast to non-necrotizing corneas, those with necrotizing HSK showed severe stromal scarring, inflammatory infiltration, and thinning. Additionally, most necrotizing lesions (77.7%) affected the visual axis and had a higher density (P = 0.01). CONCLUSION: Active HSK is characterized by significant epithelial and stromal thickening and the inactive disease manifests epithelial remodeling at sites of stromal thinning due to scarring. Necrotizing keratitis is characterized by distorted corneal architecture, substantial stromal inflammatory infiltration, and thinning. In vivo SD-OCT analysis permitted a better understanding of the inflammatory and repair mechanisms occurring in this blinding corneal disease.

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.