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.

Epidemiology, clinical features, and classification of 3,404 patients with uveitis: Colombian Uveitis Multicenter Study (COL-UVEA).

PURPOSE: To describe the epidemiology, clinical features, and classification of uveitis in a large cohort of Colombian patients. METHODS: Data were collected from seven ophthalmological referral centers in the four main cities in Colombia. The study included patients with a confirmed diagnosis of uveitis from January 2010 to December 2022. Information on demographics, ophthalmic examination findings, uveitis classification, and etiology was recorded. RESULTS: The study reviewed 3,404 clinical records of patients with uveitis. The mean age at diagnosis was 41.1 (SD 19.0) years, and 54.2% of the patients were female. Overall, 1,341(39.4%) were infectious, 626 (18.4%) non-infectious, and four masquerade syndromes (0.1%). The most common types of uveitis were unilateral (66.7%), acute (48.3%), and non-granulomatous (83%). Anterior uveitis was the most common anatomical localization (49.5%), followed by posterior uveitis (22.9%), panuveitis (22.3%), and intermediate uveitis (5.2%). A diagnosis was established in 3,252 (95.5%) cases; idiopathic was the most common cause (27.7%), followed by toxoplasmosis (25.3%) and virus-associated uveitis (6.4%). The age group between 30 and 50 exhibited the highest frequency of uveitis. CONCLUSION: This multicenter study comprehensively describes uveitis characteristics in Colombian patients, providing valuable insights into its demographic and clinical features. The study findings emphasize the need to continue updating the changing patterns of uveitis to improve diagnosis and treatment strategies for diseases associated with intraocular inflammation.

Enhancing Ocular Surface in Dry Eye Disease Patients: A Clinical Evaluation of a Topical Formulation Containing Sesquiterpene Lactone Helenalin.

The aim of this work was to assess the tolerability, safety, and efficacy of an ophthalmic topical formulation containing helenalin from Arnica montana and hyaluronic acid 0.4% (HA) in patients with mild-to-moderate Dry Eye Disease (DED) exhibiting positive Matrix Metalloproteinase 9 (MMP-9) test results. Tolerability and safety were evaluated in 24 healthy subjects. Participants were instructed to apply one drop of the formulation three times a day in the study eye, for 2 weeks, followed by a clinical follow-up of 21 days. Efficacy was studied in 48 DED patients randomized into Study (Group 1/receiving the studied formulation) or Control (Group 2/Receiving HA 0.4% eye lubricant) groups for 1 month. Assessments included an MMP-9 positivity test, conjunctival impression cytology (CIC), Ocular Surface Disease Index (OSDI), non-invasive film tear breakup time (NIBUT), non-invasive average breakup time (NIAvg-BUT), ocular surface staining, Schirmer's test, and meibomiography. A crossover design with an additional 1-month follow-up was applied to both groups. Healthy subjects receiving the studied formulation exhibited good tolerability and no adverse events. Regarding the efficacy study, Group 1 exhibited a statistically significant reduction in the MMP-9 positivity rate compared to Group 2 (p < 0.001). Both Group 1 and Group 2 exhibited substantial improvements in OSDI and NIBUT scores (p < 0.001). However, Group 1 demonstrated a significant improvement in NI-Avg-BUT and Schirmer's test scores (p < 0.001), whereas Group 2 did not (p > 0.05). Finally, after the crossover, the proportion of MMP-9-positive subjects in Group 1 increased from 25% to 91.6%, while Group 2 showed a significant decrease from 87.5% to 20.8%. Overall, the topical formulation containing sesquiterpene helenalin from Arnica montana and hyaluronic acid was well tolerated and exhibited a favorable safety profile. Our formulation reduces DED symptomatology and modulates the ocular surface inflammatory process; this is evidenced by the enhancement of CIC, the improvement of DED-related tear film status, and the reduction of the MMP-9 positivity rate.

Correlation and Level of Agreement between the Ocular Surface Disease Index and the Symptom Assessment in Dry Eye Questionnaires: A Survey-Based Study.

PURPOSE: The Ocular Surface Disease Index (OSDI) is the most frequently used dry eye disease (DED) questionnaire, and the Symptom Assessment iN Dry Eye (SANDE) is the simplest and quickest to apply. We analyze the correlation and level of agreement between these two questionnaires in a large DED heterogeneous population to evaluate their performance and potential interchangeability. METHODS: Prospective, multicenter longitudinal survey-based study performed on patients diagnosed with DED by 99 ophthalmologists from 20/32 Mexican states. Questionnaires were applied in two consecutive visits to analyze the correlation between OSDI and SANDE to evaluate patients with DED clinically. Level of agreement was evaluated with Bland-Altman analysis, and internal consistency of instruments was evaluated individually and combined with Cronbach's alpha index. RESULTS: 3421 patients studied: 1996 (58.3%) women and 1425 (41.7%) men, aged 49.5 ± 15.4 years; 995 (29.1%) patients had aqueous-deficient, 1086 (31.7%) evaporative, and 1340 (39.2%) mixed DED subtypes. Normalized baseline scores were 53.7 (OSDI) and 54.1 (SANDE). After 36.3 ± 24.4 days between visits, scores were reduced to 25.2 (OSDI) and 21.8 (SANDE) points (p < .001). A positive correlation between questionnaires was found at baseline (R = 0.592; p < .001), follow-up (R = 0.543; p < .001) and change between visits (R = 0.630; p < .001). Using both questionnaires together improved the overall reliability of symptom evaluation at baseline (α = 0.7), follow-up (α = 0.7), and both (α = 0.7), compared to individual application (OSDI α = 0.5, SANDE α = 0.6)-the same improvements applied to all DED subtypes. Bland-Altman analysis revealed a differential bias of -0.41% at baseline and +3.6% at follow-up visits between OSDI and SANDE. CONCLUSIONS: We validated the correlation (high precision) between questionnaires in a large-scale population, demonstrating improved reliability (high accuracy) in evaluating DED when used together, challenging their interchangeable use. These results open a venue to improve recommendations toward a more precise and accurate diagnostic and therapeutic evaluation of DED by using OSDI and SANDE concurrently.

Customizable Collagen Vitrigel Membranes and Preliminary Results in Corneal Engineering.

Corneal opacities are a leading cause of visual impairment that affect 4.2 million people annually. The current treatment is corneal transplantation, which is limited by tissue donor shortages. Corneal engineering aims to develop membranes that function as scaffolds in corneal cell transplantation. Here, we describe a method for producing transplantable corneal constructs based on a collagen vitrigel (CVM) membrane and corneal endothelial cells (CECs). The CVMs were produced using increasing volumes of collagen type I: 1X (2.8 µL/mm2), 2X, and 3X. The vitrification process was performed at 40% relative humidity (RH) and 40 °C using a matryoshka-like system consisting of a shaking-oven harboring a desiccator with a saturated K2CO3 solution. The CVMs were characterized via SEM microscopy, cell adherence, FTIR, and manipulation in an ex vivo model. A pilot transplantation of the CECs/CVM construct in rabbits was also carried out. The thickness of the CVMs was 3.65-7.2 µm. The transparency was superior to a human cornea (92.6% = 1X; 94% = 2X; 89.21% = 3X). SEM microscopy showed a homogenous surface and laminar organization. The cell concentration seeded over the CVM increased threefold with no significant difference between 1X, 2X, and 3X (p = 0.323). The 2X-CVM was suitable for surgical manipulation in the ex vivo model. Constructs using the CECs/2X-CVM promoted corneal transparency restoration.

An Oral Polyphenol Formulation to Modulate the Ocular Surface Inflammatory Process and to Improve the Symptomatology Associated with Dry Eye Disease.

Due to their antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic effects, polyphenols are first-rate candidates to prevent or treat chronic diseases in which oxidative stress-induced inflammation plays a role in disease pathogenesis. Dry eye disease (DED) is a common pathology, on which novel phenolic compound formulations have been tested as an adjuvant therapeutic approach. However, polyphenols are characterized by limited stability and solubility, insolubility in water, very rapid metabolism, and a very short half-life. Thus, they show poor bioavailability. To overcome these limitations and improve their stability and bioavailability, we evaluated the safety and efficacy of an oral formulation containing among other compounds, polyphenols and omega-3 fatty acids, with the addition of a surfactant in patients with DED. Subjects were randomly assigned to one of four study groups including the study formulation (A), placebo (P), the study formulation + eye lubricant (A + L), and placebo + eye lubricant (P + L). Patients from the A and P groups were instructed to take two capsules every 24 h, while patients in the L groups also added one drop of lubricant twice a day for 12 weeks as well. Regarding safety, non-ocular abnormalities were observed during study formulation therapy. Liver function tests did not show any statistically significant difference (baseline vs. week 4). Concerning efficacy, there was a statistically significant difference between baseline, month 1, and month 3 in the OSDI (Ocular Surface Disease Index) test results in both treatment groups (group A and group A + L). Furthermore, both groups showed statistically significant differences between baseline and month 3 regarding the non-invasive film tear breakup time (NIF-BUT) score and a positive trend related to Shirmer's test at month 3. The non-invasive average breakup time (NIAvg-BUT) score showed a statistically significant difference at month 3 when compared with baseline in the A + L group. The P + L group showed a statistically significant difference in terms of the OSDI questionary between baseline and month 3. Regarding the lissamine green staining, the A + L group showed a statistical difference between baseline and month 3 (p = 0.0367). The placebo + lubricant group did not show statistically significant differences. Finally, the placebo group did not show any data with statistically significant differences. Consequently, this polyphenol formulation as a primary treatment outperformed the placebo alone, and the polyphenol oral formulation used as an adjuvant to artificial tears was superior to the combination of the placebo and the artificial tears. Thus, our data strongly suggest that this polyphenol oral formulation improves visual strain symptoms and tear film status in patients with mild to moderate DED.

Dry eye disease, a prominent manifestation of systemic autoimmune disorders.

OBJECTIVES: Dry eye disease (DED) is arguably the most frequent ocular disease encountered in ophthalmic clinical practice. DED is frequently an underestimated condition causing a significant impact on visual function and quality of life. Many systemic autoimmune diseases (SAIDs) are related to moderate to severe DED. The main objective of this review is to enhance the awareness among ophthalmologists of the potential association of an underlying SAID in a high-risk patient with DED. METHODS: An exhaustive literature search was performed in the National Library of Medicine's Pubmed, Scopus, Web of Science, and Google Scholar databases for all English language articles published until November 2021. The main keywords included "dry eye disease" associated with autoimmune, connective tissue, endocrine, gastrointestinal, hematopoietic, vascular, and pulmonary diseases. Case reports, series, letters to the editor, reviews, and original articles were included. RESULTS: Although DED is frequently associated with SAIDs, its diagnosis is commonly delayed or missed, producing significant complications, including corneal ulceration, melting, scleritis, uveitis, and optic neuritis resulting in severe complications detrimental to visual function and quality of life. SAID should be suspected in a woman, 30 to 60 years old with a family history of autoimmunity, presenting with DED symptoms and extraocular manifestations including arthralgias, dry mouth, unexplained weight and hair loss, chronic fatigue, heat or cold intolerance, insomnia, and mood disorders. CONCLUSIONS: Establishing the correct diagnosis and treatment of DED associated with SAIDs is crucial to avoid its significant burden and severe ocular complications.

The impact of central foveal thickness and integrity of the outer retinal layers in the visual outcome of uveitic macular edema.

BACKGROUND: To analyze the relationship between the central foveal thickness (CFT) and the integrity of the ellipsoid portion of inner segments (EPIS) and interdigitating zone (IZ) retinal layers in the visual outcome of uveitic macular edema (UME). METHODS: Prospective, observational, and cross-sectional study of eyes with UME. Spectral-domain optical coherence tomography (SD-OCT) macular morphological pattern, CFT, and integrity of the outer retinal layers were analyzed. We arranged the data by EPIS or IZ integrity and contrasted it with student t-test (quantitative variables) and Fisher exact test or χ² distribution (categorical variables) to evaluate visual impairment and retinal measures. Receiver operator curve (ROC) estimation and logistic regression (probit) assessed if the sample´s variance could be associated with IZ or EPIS integrity. RESULTS: We included 145 SD-OCT macular scans from 45 patients at different stages of UME. Cystoid macular edema (CME) increased the risk of severe (P ≤ 0.0162) and moderate visual loss (P ≤ 0.0032). The highest CFT values occurred in patients with moderate (478.11 ± 167.62 µm) and severe (449.4 ± 224.86 µm) visual loss. Of all morphological patterns of macular edema, only CME showed a statistically significant relationship with severe visual impairment (44.92%, p = 0.0035, OR 4.29 [1.62-11.4]). Likewise, an increased probability of severe visual loss correlated negatively with both, IZ (37.93%, P ≤ 0.001, OR 10.02) and EPIS (38.98%, P ≤ 0.001, OR 13.1) disruption. A CFT > 337 µm showed a higher probability of IZ (AUROC = 0.7341, SEN 77.59%, ESP 65.52) and EPIS (AUROC = 0.7489, SEN 76.37%, ESP 65.12%) loss of integrity. Moreover, when BCVA reached 0.44 LogMAR (≤ 20/50 Snellen eq.), it was more likely to have IZ (AUROC = 0.8706, ESP 88.51%, SEN 77.59%) and EPIS (AUROC = 0.8898, ESP 88.3%, SEN 76.27) disruption. CONCLUSIONS: Significantly increased CFT has a higher probability for EPIS and IZ disruption, which significantly increases the risk for irreversible visual loss in eyes with UME. Evaluating these layers' integrity by optical coherence tomography helps predict the visual outcome and make the right therapeutic decisions. Trial registration The study was registered on April 13, 2020, at the Instituto Tecnologico y de Estudios Superiores de Monterrey Research Committee (License No. COFEPRIS 20 CI 19 039 002), project registration No. P000338-CAVICaREMU-CI-CR002, and the Ethics Committee (License No. CONBIOETICA 19 CEI 011-2016-10-17), project registration No. P000338-CAVICaREMU-CEIC-CR002.

Pigment dispersion syndrome and its implications for glaucoma.

Pigment dispersion syndrome (PDS) represents a clinical spectrum of a relatively common and usually underdiagnosed phenomenon produced by spontaneous pigment dispersion from the iris into the anterior segment. PDS is often bilateral, has no gender predisposition, and presents at a young age, particularly in myopes. Although most patients experiencing an episode of pigment dispersion are asymptomatic, extreme photophobia, ocular pain, redness, and blurred vision may occur. Other characteristic signs are iridolenticular contact, concave iris configuration, 360° peripheral iris transillumination, and pigment deposition on the anterior chamber angle or the corneal endothelium (Krukenberg spindle). Early PDS diagnosis is crucial to detect patients with pigment-related ocular hypertension (POHT) that can eventually lead to pigmentary glaucoma (PG). The latter represents a sight-threatening condition in which mechanical, environmental, and genetic factors contribute to optic nerve damage. In this review, we update the pathogenic mechanisms involved in the clinical spectrum of the disease. We describe its clinical presentation, ophthalmologic manifestations, and complications, including the factors influencing the development of POHT and PG. Because PDS has variable clinical presentations that lead to misdiagnoses, we emphasize the differential diagnosis and the actual therapeutic strategies according to disease status.

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.