Case report: Longitudinal evaluation and treatment of a melanoma-associated retinopathy patient.

Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome associated with cutaneous metastatic melanoma in which patients develop vision deficits that include reduced night vision, poor contrast sensitivity, and photopsia. MAR is caused by autoantibodies targeting TRPM1, an ion channel found in melanocytes and retinal ON-bipolar cells (ON-BCs). The visual symptoms arise when TRPM1 autoantibodies enter ON-BCs and block the function of TRPM1, thus detection of TRPM1 autoantibodies in patient serum is a key criterion in diagnosing MAR. Electroretinograms are used to measure the impact of TRPM1 autoantibodies on ON-BC function and represent another important diagnostic tool for MAR. To date, MAR case reports have included one or both diagnostic components, but only for a single time point in the course of a patient's disease. Here, we report a case of MAR supported by longitudinal analysis of serum autoantibody detection, visual function, ocular inflammation, vascular integrity, and response to slow-release intraocular corticosteroids. Integrating these data with the patient's oncological and ophthalmological records reveals novel insights regarding MAR pathogenesis, progression, and treatment, which may inform new research and expand our collective understanding of the disease. In brief, we find TRPM1 autoantibodies can disrupt vision even when serum levels are barely detectable by western blot and immunohistochemistry; intraocular dexamethasone treatment alleviates MAR visual symptoms despite high levels of circulating TRPM1 autoantibodies, implicating antibody access to the retina as a key factor in MAR pathogenesis. Elevated inflammatory cytokine levels in the patient's eyes may be responsible for the observed damage to the blood-retinal barrier and subsequent entry of autoantibodies into the retina.

Case Report: Longitudinal Evaluation and Treatment of a Melanoma-Associated Retinopathy Patient.

Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome associated with cutaneous metastatic melanoma in which patients develop vision deficits that include reduced night vision, poor contrast sensitivity, and photopsia. MAR is caused by autoantibodies targeting TRPM1, an ion channel found in melanocytes and retinal ON-bipolar cells (ON-BCs). The visual symptoms arise when TRPM1 autoantibodies enter ON-BCs and block the function of TRPM1, thus detection of TRPM1 autoantibodies in patient serum is a key criterion in diagnosing MAR. Electroretinograms are used to measure the impact of TRPM1 autoantibodies on ON-BC function and represent another important diagnostic tool for MAR. To date, MAR case reports have included one or both diagnostic components, but only for a single time point in the course of a patient's disease. Here, we report a case of MAR supported by longitudinal analysis of serum autoantibody detection, visual function, ocular inflammation, vascular integrity, and response to slow-release intraocular corticosteroids. Integrating these data with the patient's oncological and ophthalmological records reveals novel insights regarding MAR pathogenesis, progression, and treatment, which may inform new research and expand our collective understanding of the disease. In brief, we find TRPM1 autoantibodies can disrupt vision even when serum levels are barely detectable by western blot and immunohistochemistry; intraocular dexamethasone treatment alleviates MAR visual symptoms despite high levels of circulating TRPM1 autoantibodies, implicating antibody access to the retina as a key factor in MAR pathogenesis. Elevated inflammatory cytokine levels in the patient's eyes may be responsible for the observed damage to the blood-retinal barrier and subsequent entry of autoantibodies into the retina.

Locality is the strongest predictor of expert performance in image-based differentiation of bacterial and fungal corneal ulcers from India.

PURPOSE: This study sought to identify the sources of differential performance and misclassification error among local (Indian) and external (non-Indian) corneal specialists in identifying bacterial and fungal keratitis based on corneal photography. METHODS: This study is a secondary analysis of survey data assessing the ability of corneal specialists to identify acute bacterial versus fungal keratitis by using corneal photography. One-hundred images of 100 eyes from 100 patients with acute bacterial or fungal keratitis in South India were previously presented to an international cohort of cornea specialists for interpretation over the span of April to July 2021. Each expert provided a predicted probability that the ulcer was either bacterial or fungal. Using these data, we performed multivariable linear regression to identify factors predictive of expert performance, accounting for primary practice location and surrogate measures to infer local fungal ulcer prevalence, including locality, latitude, and dew point. In addition, Brier score decomposition was used to determine experts' reliability ("calibration") and resolution ("boldness") and were compared between local (Indian) and external (non-Indian) experts. RESULTS: Sixty-six experts from 16 countries participated. Indian practice location was the only independently significant predictor of performance in multivariable linear regression. Resolution among Indian experts was significantly better (0.08) than among non-Indian experts (0.01; P < 0.001), indicating greater confidence in their predictions. There was no significant difference in reliability between the two groups ( P = 0.40). CONCLUSION: Local cornea experts outperformed their international counterparts independent of regional variability in tropical risk factors for fungal keratitis. This may be explained by regional characteristics of infectious ulcers with which local corneal specialists are familiar.

A Vascularized Iris Mass in Ocular Syphilis: A Case Report and Review of Literature.

PURPOSE: To describe features of a syphilitic vascularized iris mass on multimodal imaging and its resolution after penicillin treatment. METHODS: Observational case report and literature review of syphilitic iris masses. RESULTS: A 43-year-old woman presented with a unilateral vascularized tan iris mass in the setting of bilateral panuveitis that occurred along with bilateral papillitis, cystoid macular edema and retinal vasculitis. Laboratory work-up confirmed a diagnosis of syphilis. Ultrasound biomicroscopy (UBM) of the iris mass showed parapupillary hyperechoic full-thickness iris stromal thickening with small intrinsic circular lumens without cyst or ciliary body extension, while the anterior segment optical coherence tomography (AS-OCT) demonstrated a hyperreflective mass with deep iris extension and partial hyporeflective rim. Following treatment, the mass fully resolved without residual sequela. A review of literature identified 11 additional cases of syphilitic iris masses in the English literature from 1915 to present. Their presentations and clinical courses were reviewed herein. CONCLUSIONS: This report characterizes a syphilitic iris mass on slit-lamp photography, iris fluorescein angiography, UBM and AS-OCT; depicts key characteristics of syphilitic iris masses; and highlights the need for close inspection of the iris mass as an uncommon sign of ocular syphilis.

Late diagnosis of Cutibacterium acnes (formerly Proprionibacterium acnes) endophthalmitis and the importance of dual testing with bacterial culture and polymerase chain reaction.

PURPOSE: To describe two cases of C. acnes endophthalmitis that reinforce the importance of performing both bacterial culture and 16s polymerase chain reaction when the causative pathogen is unclear or difficult to culture, such as C. acnes. A case of C. acnes endophthalmitis complicated by sub-buckle scleral perforation is illustrated with intraoperative photography. METHODS: Two-case series. RESULTS: Case 1 describes a case of C. acnes endophthalmitis in a longstanding pseudophakic patient following multiple vitrectomies for recurrent retinal detachment, complicated by sub-buckle scleral perforation. Bacterial culture revealed C. acnes while 16s PCR was negative. Conversely, Case 2 demonstrates a case of chronic endophthalmitis diagnosed one year following cataract surgery. PCR (with repeat tap for confirmation) revealed C. acnes with a negative culture. CONCLUSION: When the causative pathogen of endophthalmitis is unclear, dual testing of microbial culture and C. acnes 16s PCR improves the diagnostic yield of investigations for fastidious pathogens. C. acnes can present as an indolent or virulent endophthalmitis.

Diagnosis and Characteristics of Presentation of Tubulointerstitial Nephritis and Uveitis Syndrome During the COVID-2019 Pandemic.

PURPOSE: To compare the diagnosis and clinical features of tubulointerstitial nephritis and uveitis syndrome (TINU) before and during the COVID-19 pandemic. METHODS: Retrospective chart review. RESULTS: Before the COVID-19 pandemic (March 2017 to March 2019), 1/561 (0.18%) new patient was diagnosed with TINU. During the pandemic (March 2020 to March 2022), 15/581 (2.58%) new patients were diagnosed with TINU. We found a significant increase in TINU cases during the pandemic (P=0.0005). Various posterior segment findings were observed in 2/3 (66.7%) patients before the pandemic and 13/15 (86.7%) patients during the pandemic, including disc edema, chorioretinal scars, disc leakage, and peripheral vascular leakage. CONCLUSION: This is the first study reporting an increased number of TINU during the COVID-19 pandemic. With most of the American population now exposed to COVID-19, a large multi-center epidemiological study would be helpful to investigate any association of COVID-19 disease or vaccination with TINU in recent years.

Comparison of Comorbid Associations and Ocular Complications in Herpes Simplex and Zoster Keratitis.

A retrospective chart review examined adult patients with herpes simplex (HSV) and zoster (HZO) keratitis at a single institution. Patients who suffered a poor outcome (defined as visually significant corneal scarring, neurotrophic keratitis, secondary glaucoma, or requiring corneal surgery) were identified and each outcome type was analyzed in relation to age, sex, diabetes mellitus, immunosuppression, and a prior history of ≥2 ocular procedures.Advanced age, diabetes mellitus, and a prior history of ≥2 ocular procedures may be risk factors for poor outcomes in HSV, but not HZO, keratitis. In HSV, older age and DM were specifically associated with visually significant corneal scarring, while older age and male sex were associated with secondary glaucoma. Future prospective studies are warranted to determine the ideal management (including prophylaxis) in patients with these characteristics.

Potentiating aminoglycoside antibiotics to reduce their toxic side effects.

The lack of new antibiotics necessitates the improvement of existing ones, many of which are limited by toxic side effects. Aminoglycosides, antibiotics with excellent activity and low bacterial resistance, are hampered by dose-dependent toxic effects in patients (nephrotoxicity, ototoxicity). High antibiotic concentrations are often required to treat dormant, non-dividing bacteria, though previous studies show that aminoglycosides can be activated against such bacteria by specific metabolites. Here, we employed this mechanism to greatly boost the activity of low concentrations of aminoglycosides against prevalent Gram-negative pathogens (Escherichia coli, Salmonella enterica, and Klebsiella pneumoniae), suggesting that less toxic drug concentrations might be used effectively in patients. We go on to show that this effect improved treatment of biofilms, did not increase aminoglycoside resistance, and was due to the generation of proton-motive force (PMF). By single-cell microscopy, we demonstrate that stationary-phase cells, while non-dividing, actively maintain a growth-arrested state that is not reversed by metabolite addition. Surprisingly, within starved populations, we observed rare cells (3%) that divided without added nutrients. Additionally, we discovered that mannitol could directly protect human kidney cells from aminoglycoside cytotoxicity, independent of the metabolite's effect on bacteria. This work forwards a mechanism-based strategy to improve existing antibiotics by mitigating their toxic side effects.

Ischemic optic neuropathy after Descemet-stripping automated endothelial keratoplasty.

An 82-year-old woman presented with a failed Descemet-stripping automated endothelial keratoplasty (DSAEK) in her right eye performed a month earlier. The patient underwent uneventful repeat DSAEK. Six days after the procedure, the patient was found to have an afferent pupillary defect and optic nerve swelling in her right eye on fundoscopy and optical coherence tomography. A comprehensive workup, including bilateral temporal artery biopsies and magnetic resonance imaging, for vasculitic etiologies was negative. A diagnosis of nonarteritic anterior ischemic optic neuropathy (NAION) was made. Although NAION has been reported after various ocular surgeries, to the authors' knowledge, this is the first reported case of NAION after uneventful corneal transplantation. Therefore, NAION should be considered a rare complication of corneal transplantation surgery. Meticulous preoperative and postoperative evaluation, including an attentive pupillary and dilated fundus examination, are essential in assessing a patient's risk factors for this condition and monitoring for its occurrence in the perioperative period.