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Purpose: Artificial intelligence (AI) is often trained on images without ocular co‑morbidities, limiting its generalizability. This study aims to evaluate the accuracy of a convolutional neural network (CNN) applied to color fundus photos (CFPs) with simulated cataracts (SCs) in detecting diabetic retinopathy (DR). Methods: A database of 3662 CFPs (from Asia Pacific Tele‑Ophthalmology Society (APTOS) 2019) was used. Using transfer learning, a CNN was trained to classify the training images as either DR or non‑DR. The CNN was then applied to classify the testing images after an SC was applied, using varying degrees of Gaussian blur. Results: Accuracy without SC was 97.0%, sensitivity (Sn) 95.7%, specificity (Sp) 98.3%. For mild SC, accuracy was 93.1%, Sn 91.8%, Sp 94.3%. For moderate SC, accuracy was 62.8%, Sn 31.4%, Sp 95.2%. For severe SC, accuracy was 53.5%, Sn 11.8%, Sp 96.5%. Conclusion: SCs significantly impaired AI accuracy. To prepare AI for clinical use, cataracts and other real‑world clinical challenges affecting image quality must be accounted for. [ABSTRACT FROM AUTHOR]

Purpose: Previous literature has investigated opioid prescription trends in ophthalmology at large, however, little has been done looking at differences between subspecialties. We evaluate if significant trends exist among subspecialties in opioid prescribing patterns. This study aims to illuminate potential over-usage of opioids in ophthalmology that could compromise patient quality of life. Methods: Medicare data and "National Plan and Provider Enumeration System (NPPES) Downloadable File" were queried for cases of ophthalmologists with nonsuppressed opioid prescription data from 2014 to 2019. Ophthalmologists with no subspecialty code or missing regional, gender, degree, or graduation information were excluded. Chi-squared analysis, analysis of variance, t-tests, and multivariate logistic regression were utilized. Results: Five thousand one hundred forty-three physician records were included in analysis, 450 of which were by cornea subspecialists. Most cornea cases were male, graduated before 2005, and practiced in the South. All subspecialties had a significantly increased likelihood of making opioid claims and higher prescription rates compared with cornea (P < 0.050) besides glaucoma (P = 0.357). Only oculoplastics had significantly increased likelihood of greater total supply of opioids compared with cornea (odds ratio [OR] = 22.195, 95% confidence interval [CI] = 12.209–40.350, P < 0.001), while pediatrics (OR = 4.036, 95% CI = 1.377–11.831, P = 0.011) and neuro-ophthalmology (OR = 4.158, 95% CI = 1.237–13.975, P = 0.021) in addition to oculoplastics (OR = 64.380, 95% CI = 26.306–157.560, P < 0.001) were predicted to have significantly greater opioid beneficiaries. Males, the South/Midwest, and graduating before 2005, all were generally associated with increased likelihood of greater total opioid claims, supply, beneficiaries, and prescription rate (P < 0.050). Conclusion: Subspecialty, demographic, chronological, and regional trends exist for opioid prescribing patterns in ophthalmology. [ABSTRACT FROM AUTHOR]

Antibody-drug conjugates (ADCs) are a growing class of chemotherapeutic agents for the purpose of treating cancers that often have relapsed or failed first- and second-line treatments. ADCs are composed of extremely potent cytotoxins with a variety of side effects, one of the most significant being ocular toxicity. The available literature describes these toxicities as varying in severity and in incidence, although with disparate methods of evaluation and management. Some of the most common toxicities include microcyst-like epithelial keratopathy and dry eye. We discuss proposed mechanisms of ocular toxicity and describe the reports that mention these toxicities. We focus on ADCs with the most published literature and the most significant effects on ocular tissue. We propose areas for further investigation and possible ideas of future management. We provide a comprehensive look at the reports of ADCs in current literature to better inform clinicians on an expanding drug class. [ABSTRACT FROM AUTHOR]

Purpose: Povidone-iodine (PVI), also known as Betadine, is a widely used antiseptic agent used in several fields of medicine. In ophthalmology, it is applied as a preoperative antiseptic to prevent infectious complications that can result from surgical procedures. PVI's safety and efficacy have been extensively studied and represented in the literature; however, the incidence of adverse effects has been reported in conjunction. The aim of this paper is to compile information regarding PVIs use, safety profile, adverse effects, and possible alternatives through a review of the existing literature. Methods: Literature was compiled utilizing the database PubMed and Google Scholar using specified keywords with a total of 86 reviewed articles, after excluding search results that did not meet the inclusion criteria. Results: While the allergic potential to PVI is a highly contested topic, there are several nonallergic adverse effects of PVI that should not be overlooked. These effects include chemical burn, cytotoxic effects, and general patient discomfort. In light of these adverse effects, alternatives to PVI may be considered. However, there has been little research identifying feasible alternatives in preoperative intraocular procedures. Alternatives including chlorhexidine, polyhexamethylene biguanide (polyhexanide), and octenidine were identified as potential substitutes for PVI. Conclusions: Further study is needed to provide robust evidence regarding the efficacy profiles of these alternatives in comparison with PVI and to demonstrate comparable tolerance to PVI in intraocular procedures. [ABSTRACT FROM AUTHOR]

The article discusses corneal nerve alterations in dry eye-associated ocular surface disease. It describes how sensory nerves in the cornea transmit signals to the brain stem which is then transmitted to the lacrimal gland and eventually drives tear production and secretion. A disruption in the process through damage to the neural circuit interrupts normal regulation of lacrimal gland secretion and causes dry eye disease.

Purpose. To investigate whether corneal graft survival could be improved by topical or subconjunctival bevacizumab in a murine model of vascularized high-risk corneal transplantation. Methods. Before corneal transplantation, intrastromal sutures were placed for 2 weeks in the corneas of BALB/c mice, inducing intense angiogenesis. Allogeneic corneal transplantation was performed using C57BL/6 donor mice. Topical bevacizumab (2.5%) was delivered 3 times a day for 3 weeks in one treatment group, and 0.02 mL (0.5 mg) bevacizumab was injected subconjunctivally at days 0, 4, 8, and 15 after transplantation in the other treatment group. The control group received no treatment. Grafts were examined twice a week for 8 weeks by slit-lamp microscopy and were photographed once a week by slit-lamp digital camera and scored for opacity. For assessment of corneal neovascularization (NV), a quantitative method was used to measure three primary metrics including neovascular area, vessel caliber, and neovessel invasion area. Results. Both topical and subconjunctival bevacizumab treatment reduced neovascular area and vessel caliber; however, the regression of corneal NV was more profound when treated subconjunctivally. The mean percentage reduction of neovascular area was 55% (P < 0.05) by week 8 in the subconjunctival treatment group and 33% (P = 0.15) in the topical group. Only subconjunctival bevacizumab treatment resulted in significant regression of neovessel invasion area (P < 0.05). All corneal transplants in both the control and the topical groups were rejected by 4 weeks after transplantation. However, in the subconjunctival treatment group, 33% of corneal grafts survived (P < 0.01). Conclusions. Subconjunctival bevacizumab may offer an adjunctive measure to conventional therapies in preventing graft rejection in high-risk corneal transplantation.

Purpose Herpes zoster ophthalmicus (HZO), thought to be a unilateral disease, results in loss of corneal sensation, leading to neurotrophic keratopathy. This study aimed to analyze bilateral corneal nerve changes in patients with HZO by in vivo confocal microscopy (IVCM) and their correlation with corneal sensation as a measure of nerve function. Design Prospective, cross-sectional, controlled, single-center study. Participants Twenty-seven eyes with the diagnosis of HZO and their contralateral clinically unaffected eyes were studied and compared with normal controls (n = 15). Methods In vivo confocal microscopy (Confoscan 4; Nidek Technologies, Gamagori, Japan) and corneal esthesiometry (Cochet-Bonnet; Luneau Ophthalmologie, Chartres, France) of the central cornea were performed bilaterally in all patients and controls. Patients were grouped into normal (>5.5 cm), mild (>2.5–5.5 cm), and severe (<2.5 cm) loss of sensation. Main Outcome Measures Changes in corneal nerve density, total nerve number, main nerve trunks, branching, and tortuosity were evaluated after IVCM and were correlated to corneal sensation, disease duration, and number of recurrences. Results Eyes with herpes zoster ophthalmicus had a significant (P<0.001) decrease in total nerve length (595.8±358.1 vs. 2258.4±989.0 μm/frame), total number of nerves (5.4±2.8 vs. 13.1±3.8), number of main nerve trunks (2.3±1.1 vs. 4.7±1.2), and number of nerve branches (3.2±2.3 vs. 8.4±3.7) as compared with controls. In the contralateral clinically unaffected eyes, total nerve length (1053.1±441.4 μm/frame), total number of nerves (8.3±2.9), and main nerve trunks (3.1±1.0) also were decreased significantly as compared with controls (P<0.01). Reduced nerve density, total nerve count, main trunks, and tortuosity was correlated significantly with corneal sensation across all subgroups (P<0.001). Conclusions Patients with unilateral HZO demonstrated a profound and significant bilateral loss of the corneal nerve plexus as compared with controls, demonstrating bilateral changes in a clinically unilateral disease. Loss of corneal sensation strongly correlated with subbasal nerve plexus alterations as shown by IVCM.

Purpose To analyze the morphology of corneal epithelial cells and keratocytes by in vivo confocal microscopy (IVCM) in patients with herpes simplex keratitis (HSK) as associated with corneal innervation. Design Prospective, cross-sectional, controlled, single-center study. Participants Thirty-one eyes with the diagnosis HSK and their contralateral clinically unaffected eyes were studied and compared with normal controls (n = 15). Methods In vivo confocal microscopy (Confoscan 4; Nidek Technologies, Gamagori, Japan) and corneal esthesiometry (Cochet-Bonnet; Luneau Ophthalmologie, Chartres, France) of the central cornea were performed bilaterally in all patients and controls. Patients were grouped into normal (>5.5 cm), mild (>2.5–5.5 cm), and severe (<2.5 cm) loss of sensation. Main Outcome Measures Changes in morphology and density of the superficial and basal epithelial cells, as well as stromal keratocytes were assessed by two masked observers. Changes were correlated to corneal sensation, number of nerves, and total length of nerves. Results There was a significant and gradual decrease in the density of superficial epithelial cells in HSK eyes, with 852.50±24.4 cells/mm2 in eyes with severe sensation loss and 2435.23±224.3 cells/mm2 in control eyes (p=0.008). Superficial epithelial cell size was 2.5-fold larger in HSK eyes (835.3 μm2) as compared to contralateral or normal eyes (407.4 μm2; p= 0.003). A significant number of hyperreflective desquamating superficial epithelial cells were present in HSK eyes with normal (6.4%), mild (29.1%) and severe (52.2%) loss of sensation, but were absent in controls. The density of basal epithelial cells, anterior keratocytes, and posterior keratocytes did not show statistical significance between patients and controls. Changes in superficial epithelial cell density and morphology correlated strongly with total nerve length, number, and corneal sensation. Scans of contralateral eyes did not show any significant epithelial or stromal changes as compared to controls. Conclusions IVCM reveals profound HSK-induced changes in the superficial epithelium, as demonstrated by increase in cell size, decrease in cell density, and squamous metaplasia. We demonstrate that these changes strongly correlate with changes in corneal innervation.

Purpose. To determine the effect of azithromycin (AZM) in a murine model of corneal inflammation. Methods. The effect of topical AZM was studied in murine corneal inflammation. Corneal inflammation was induced by thermal cautery in BALB/c mice. Leukocyte infiltration at different time points was analyzed by flow cytometry. At set time points, real-time polymerase chain reaction was performed to quantify the expression of different inflammatory cytokine transcript in the cornea. Corneal samples were analyzed immunohistochemically for the expression of intercellular adhesion molecule-1 (ICAM-1). Corneal neovascularization (CNV) was induced by micropellet (VEGF-A) placement. Mice were then treated topically with either AZM or vehicle. CNV was evaluated morphometrically. Results. Eyes receiving AZM showed a significant decrease in corneal infiltration compared with the vehicle-treated group. AZM also significantly decreased messenger RNA expression levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and ICAM-1 in the cornea. There was no significant difference in CNV between the AZM- and vehicle-treated groups. Conclusions. After an inflammatory insult, topical AZM significantly reduced leukocyte infiltration into the cornea. This was further supported by an associated decrease in expression of IL-1β, TNF-α, and ICAM-1 in the cornea, indicating AZM may have a potential anti-inflammatory effect on corneal inflammation.

Purpose To study and correlate corneal sensation in patients with herpes simplex keratitis (HSK) with density and morphology of subbasal corneal nerves by in vivo confocal microscopy (IVCM). Design Prospective, cross-sectional, controlled, single-center study. Participants Thirty-one eyes with the diagnosis of acute (n=7) or chronic (n=24) HSK and the contralateral clinically unaffected eyes were studied and compared to normal controls (n=15). Methods IVCM (Confoscan 4, Nidek) and corneal esthesiometry (Cochet-Bonnet) of the central cornea were performed bilaterally in all patients and controls. Patients were grouped into normal (>5.5 cm), mild (>2.5 to 5.5cm) and severe (≤2.5 cm) loss of sensation. Main Outcome Measures Changes in corneal nerve density, total nerve number, main nerve trunks, branching and tortuosity were evaluated after IVCM and correlated to corneal sensation, disease duration, and number of recurrences. Results HSK eyes, as compared to controls, demonstrated significant (p<0.001) decrease in mean nerve density (448.9±409.3 vs. 2,258.4±989.0 μm/frame), total nerve number (5.2±4.5 vs. 13.1±3.8), main nerve trunks (2.3±1.6 vs. 4.7±1.2) and nerve branches (3.2 ± 4.3 vs. 9.8±3.3). In contralateral unaffected eyes, mean nerve density (992.7±465.0 μm/frame), total nerve number (7.8±3.3), and branches (4.5±2.3) were significantly decreased as compared to controls (p<0.002). Reduced nerve density, total nerve count and main trunks in HSK eyes were significantly correlated with corneal sensation across all subgroups (p<0.001). Nerve density decreased within days of infection and was correlated to frequency of episodes in patients with HSK (p<0.02). Conclusions In vivo confocal microscopy reveals that the loss of corneal sensation in HSK correlates strongly with profound diminishment of the subbasal nerve plexus after herpes simplex virus (HSV) infection. Surprisingly, the contralateral clinically unaffected eyes also demonstrated a diminishment of the subbasal nerve plexus, as compared to normal subjects, revealing bilateral nerve alteration in an apparently unilateral disease.

Background: Rheumatoid arthritis (RA) is a chronic, multisystemic disease of unknown aetiology. The main feature of RA is a symmetric, additive inflammatory arthritis of small peripheral joints. The disease is more common in women. There is some evidence about the role of sex in pathogenesis and clinical features of RA. Aim: The aim of this study is the recognition of the aspects of RA in female and male patients. Method: This study includes the RA patients referred to the RA Research Clinic of Imam Hospital, Tehran, Iran, between 1998 and 1999 of which 160 were selected. One hundred and twenty-two were female and 38 male, showing a female to male ratio of 3 : 1. Results: The mean age at the time of diagnosis of RA was 37 and 43 years in women and men respectively. The mean duration of disease before diagnosis was 8.8 years in women and 5.8 years in men. The indices of pain, limitation of movement and swelling of joints were higher in women, but only for the pain indices was the difference between the two sexes stastistically significant. No statistically significant difference in joint deformity was found between the two sexes but erosive joint lesions were more common in women. Involvement of the small joints of the upper limbs was more prevalent in women but hip and cervical spine involvement was more frequent in men. Considering extra-articular involvement, rheumatoid nodules, pulmonary and cardiac involvement and vasculitis was more prevalent in men but only for cardiac involvement was a statistically significant difference between the two sexes found. Rheumatoid factor was positive in 60% of both sexes. There was no statistically significant differences in lab tests and treatment strategy between the two sexes. Conclusion: RA has a more severe course and worse prognosis in women; however, extra-articular involvement is more frequent in men. [ABSTRACT FROM AUTHOR]

The article presents several letters including letter to the editor in response to the article "Short-term topical bevacizumab in the treatment of stable corneal neovascularization" by Sheng-Fu Cheng alongwith the response from the author in the July, 2013 issue.