A Severe and Prolonged Case of Ocular Monkeypox Without Systemic Manifestations.

PURPOSE: The objective of this study was to present a rare case of prolonged and severe ocular monkeypox virus infection in the absence of systemic manifestations. METHODS: This was a single case report. RESULTS: A 60-year-old man, having been symptomatic for 9 days, presented with several umbilicated, ulcerated papules on the left cheek, left side of the nose, and left upper eyelid, along with marked follicular conjunctivitis and multiple conjunctival ulcerations. Two weeks after presentation, he developed an irregular, 360° circumferential opacity in the peripheral cornea that progressed to a large epithelial defect with corneal thinning. Although the initial eyelid lesions and conjunctivitis quickly resolved, the patient experienced nonresolving corneal inflammation manifest with peripheral corneal thinning, epithelial defects, and stromal keratitis. Four months after presentation, with the presumptive diagnosis of peripheral ulcerative keratitis, the patient was treated with intravenous steroids and immunosuppressive treatment, after which the ocular surface inflammation improved. However, the inflammation recurred 12 weeks later, and the patient developed severe perilimbal necrotizing conjunctivitis, followed by recurrence of ulcerated nodular eyelid lesions. Eight months after presentation, nucleic acid amplification tests from eyelid lesion swabs returned positive for nonvariola Orthopoxviruses, which led to the diagnosis of mpox. Within 2 weeks of beginning antiviral treatment with systemic tecovirimat and cidofovir and topical trifluridine, the eyelid lesions, conjunctivitis, and corneal inflammation resolved. CONCLUSIONS: We present an unusual and challenging case of ocular mpox with severe ocular surface inflammation including peripheral corneal thinning and epithelial defects, without systemic disease. Initiation of antiviral treatment resulted in a quick resolution of the ocular disease.

Effectiveness of the Dexamethasone Implant in Lieu of Oral Corticosteroids in Intermediate and Posterior Uveitis Requiring Immunosuppression.

PURPOSE: To evaluate dexamethasone intravitreal implant effectiveness in lieu of high-dose oral prednisone for short-term treatment of noninfectious intermediate and posterior uveitis in patients requiring immunosuppression. METHODS: This is a proof-of-concept, open-label, non-comparative clinical trial with 12-month follow-up. The primary outcome was uveitis control without additional prednisone at 6 and 12 months. Secondary outcomes were need for multiple implants or additional prednisone, and safety data. RESULTS: 20 patients (28 eyes) were enrolled- 16 eyes had control by 6 months; 20 by 12 months. No patients required high-dose prednisone. 6 patients enrolled on prednisone: 2 stopped; 4 tapered to 7.5 mg daily or less by 12 months. 16 eyes required multiple implants; five required cataract surgery; 12 required drops to control IOP; 2 underwent glaucoma surgery. CONCLUSIONS: The dexamethasone implant was effective in lieu of high-dose prednisone although the majority required multiple implants. All patients decreased or discontinued prednisone during follow-up.

Corneal Sarcoidosis: Diffuse Stromal Granulomatous Inflammation in a Patient With Sarcoidosis.

PURPOSE: The purpose of this study was to present a case of diffuse noncaseating granulomas involving the corneal stroma in a patient with ocular and pulmonary sarcoidosis. METHODS: This was a single case report. RESULTS: A 31-year-old female patient presented with a 6-year history of panuveitis of the right eye along with a history of pulmonary sarcoidosis and a conjunctival biopsy of the right eye that was reported as positive for sarcoidosis. At presentation to our clinic, the patient had band keratopathy, vascularization of the inferonasal cornea, and active anterior uveitis of the right eye. When the patient returned for a follow-up of 15 months after the initial presentation, the cornea of the right eye exhibited widespread stromal scarring and vascularization. Because of the corneal scarring, the patient underwent an implantation of a Boston type 1 keratoprosthesis in the right eye. Histopathological examination of the host corneal tissue removed at the time of the keratoprosthesis procedure revealed extensive noncaseating granulomas in the deep corneal stroma. The patient underwent penetrating keratoplasty 8 months later, and histopathological examination again demonstrated noncaseating granulomas, this time at the edges of the donor corneal graft used during the keratoprosthesis implantation. CONCLUSIONS: We present the histopathological evidence of sarcoidosis involving the corneal stroma. Interestingly, the stromal keratitis also subsequently involved the donor cornea tissue after the patient underwent a keratoprosthesis implantation. It seems that sarcoidosis is a rare cause of stromal keratitis.

Identification of microbial agents in tissue specimens of ocular and periocular sarcoidosis using a metagenomics approach.

Background: Metagenomic sequencing has the potential to identify a wide range of pathogens in human tissue samples. Sarcoidosis is a complex disorder whose etiology remains unknown and for which a variety of infectious causes have been hypothesized. We sought to conduct metagenomic sequencing on cases of ocular and periocular sarcoidosis, none of them with previously identified infectious causes. Methods: Archival tissue specimens of 16 subjects with biopsies of ocular and periocular tissues that were positive for non-caseating granulomas were used as cases. Four archival tissue specimens that did not demonstrate non-caseating granulomas were also included as controls. Genomic DNA was extracted from tissue sections. DNA libraries were generated from the extracted genomic DNA and the libraries underwent next-generation sequencing. Results: We generated between 4.8 and 20.7 million reads for each of the 16 cases plus four control samples. For eight of the cases, we identified microbial pathogens that were present well above the background, with one potential pathogen identified for seven of the cases and two possible pathogens for one of the cases. Five of the eight cases were associated with bacteria ( Campylobacter concisus, Neisseria elongata, Streptococcus salivarius, Pseudopropionibacterium propionicum, and Paracoccus yeei), two cases with fungi ( Exophiala oligosperma, Lomentospora prolificans and Aspergillus versicolor) and one case with a virus (Mupapillomavirus 1). Interestingly, four of the five bacterial species are also part of the human oral microbiome. Conclusions: Using a metagenomic sequencing we identified possible infectious causes in half of the ocular and periocular sarcoidosis cases analyzed. Our findings support the proposition that sarcoidosis could be an etiologically heterogenous disease. Because these are previously banked samples, direct follow-up in the respective patients is impossible, but these results suggest that sequencing may be a valuable tool in better understanding the etiopathogenesis of sarcoidosis and in diagnosing and treating this disease.

MULTIMODAL IMAGING IN DIDANOSINE RETINOPATHY.

PURPOSE: To present the multimodal retinal imaging findings in didanosine retinopathy in a patient who presented 6.5 years after stopping the use of didanosine and to highlight the absence of progression during a 1.5-year follow-up. METHODS: Case report involving clinical examination, fundus photography, fundus autofluorescence, fluorescein angiography, optical coherence tomography, Goldmann kinetic perimetry, and full-field electroretinography. RESULTS: A 52-year-old patient presented with bilateral retinopathy 6.5 years after stopping didanosine having used the medication for 8.5 years. Fundus examination showed a ring-shaped zone of atrophy of the retinal pigment epithelium involving the midperiphery. On autofluorescence imaging, there was diffuse hypoautofluorescence involving the midperipheral retina in both eyes. On fluorescein angiography, there was a granular mottled pattern of diffuse hyperfluorescence in the midperiphery in both eyes, with baring of the large choroidal vessels in some areas. On Goldmann kinetic perimetry, both eyes showed marked constriction of the isopter to the I4e stimulus, and there was a temporal scotoma to the III4e target in both eyes. Full-field electroretinography showed generalized rod and cone photoreceptor dysfunction in both eyes. During a follow-up for 1.5 years, there was no evidence of progression. CONCLUSION: Patients who have used didanosine should be evaluated for the presence of retinopathy, which involves the midperipheral retina.

Disease Relapse After Drug-Free Remission in Ocular Mucous Membrane Pemphigoid.

PURPOSE: To quantitate the risk of relapse of ocular and extraocular disease among patients with mucous membrane pemphigoid (MMP) who had undergone drug-free remission. DESIGN: Retrospective, comparative, interventional case series. METHODS: There were 167 patients with biopsy-proven MMP who were seen at the Wilmer Eye Institute between November 1984 and December 2019. Among the 167 patients, 119 patients had ocular involvement and 103 of those patients received systemic treatment for MMP. The main outcome measures were the incidence of ocular remission, incidence rate of disease relapse after remission, and risk factors for disease relapse. RESULTS: Over a median follow-up time of 7 years, 74 of 103 treated patients (71.8%) experienced drug-free remission (incidence rate = 0.28/person-year [PY], 95% confidence interval [CI] 0.22-0.35/PY). Most patients (80/103, 77.7%) received cyclophosphamide therapy. Thirteen of the 74 patients (17.6%) had disease relapse after remission: 4 with ocular disease only, 4 with extraocular disease only, and 5 with both. The rate relapse of ocular MMP was 0.020/PY (95% CI 0.009-0.038/PY), and the rate of relapse of MMP at any site (ocular or extraocular site) was 0.029/PY (95% CI 0.015-0.050/PY). The use of cyclophosphamide was associated with a greater chance of remission (hazard ratio [HR] = 3.84, P < .0001) and a lower risk of relapse (HR = 0.32, P = .05) compared with other immunosuppressive drugs except for rituximab. Five patients experienced drug-free remission after rituximab therapy and none of them had relapse (median follow-up after remission = 3.6 years). When use of cyclophosphamide or rituximab was compared with all other treatments, the risk of MMP relapse at any site (HR = 0.17, P = .02) and of ocular MMP (HR = 0.11, P = .007) were significantly lower. CONCLUSIONS: Rates of relapse of MMP after drug-free remission are low but not zero; therefore, monitoring of patients remains necessary. Relapses were not observed among those patients treated with rituximab who had remission; however, follow-up duration in those patients was shorter than the whole MMP cohort and the sample size was small.

Dupilumab-Associated Conjunctivitis in Patients With Atopic Dermatitis.

PURPOSE: To report the occurrence of conjunctivitis associated with the use of dupilumab in patients with atopic dermatitis. METHODS: A retrospective small case series. RESULTS: The first case was a 56-year-old man who developed conjunctivitis 2 weeks after starting dupilumab. The second case was a 19-year-old man who developed blepharoconjunctivitis 3 months after staring dupilumab. The ocular inflammation in both cases resolved rapidly and remained controlled with topical steroid drops without necessitating the discontinuation of dupilumab. However, the second patient had already developed conjunctival cicatrization in 1 eye at the time of presentation. CONCLUSIONS: The pathophysiology and the risk factors for the development of conjunctivitis in patients who take dupilumab for atopic dermatitis are not completely understood. However, topical steroid treatment halts the inflammation effectively without discontinuation of dupilumab therapy.

Incidence and Clinical Characteristics of Ocular Involvement in Mucous Membrane Pemphigoid.

Purpose: To describe the risk of developing ocular mucous membrane pemphigoid (MMP) or a new extraocular site of MMP, and to identify risk factors for new involvement. Methods: Retrospective chart review of 162 biopsy-proven MMP patients. Results: At presentation, 109 of 162 MMP patients (67.3%) had ocular involvement and 53 patients did not. Of the 53 patients without ocular involvement at presentation followed up to 22 years, the risk of developing ocular MMP was 0.014 per person-year (PY, 95% confidence interval [CI]: 0.005/PY, 0.034/PY). The risk of developing any new location of extraocular MMP was 0.020/PY (95% CI: 0.007/PY, 0.043/PY). Smoking was a risk factor for developing an additional extraocular MMP location (hazard ratio [HR] = 4.09, p = 0.04). Conclusions: Patients presenting with extraocular MMP are at risk for developing ocular MMP, and all MMP patients are at risk for developing secondary extraocular MMP locations, although the rates were low.

Clinical Features and Incidence Rates of Ocular Complications in Patients With Retinal Vasculitis.

PURPOSE: To describe the incidence rates of visual loss and ocular complications in patients with retinal vasculitis (RV). DESIGN: Retrospective cohort study. METHODS: Clinical data were collected for 96 patients (175 eyes) diagnosed with RV from 2003 to 2013. Main outcome measures included rates of visual loss and ocular complications. Comparison of outcomes in patients with a relapsing vs nonrelapsing disease also were analyzed. RESULTS: Over a median follow-up of 44 months (range: 1-153 months), the rate of visual loss to 20/50 or worse was 0.13 per eye-year (/EY, 95% confidence interval [CI], 0.09/EY to 0.18/EY) and to 20/200 or worse was 0.06/EY (95% CI, 0.04/EY to 0.08/EY). The most common complications were cataract (0.31/EY), epiretinal membrane (0.16/EY), and recurrent macular edema (0.09/EY). Patients with a relapsing course (median number of relapses = 1, range: 1-6) appeared to have greater risk for visual loss to 20/50 (odds ratio [OR] = 2.07; 95% CI, 0.88-4.90, P = .09) and 20/200 or worse (OR = 2.49; 95% CI, 0.98-6.30, P = .05). Immunosuppressive drug therapy lowered the risk of visual loss, independent of relapsing disease course (OR = 0.79; 95% CI, 0.66-0.94, P = .01 and OR = 0.73; 95% CI, 0.57-0.93, P = .01 for the 20/50 or worse and 20/200 or worse thresholds, respectively). CONCLUSIONS: Rates of visual loss and complications among patients with RV were similar to reported rates in noninfectious uveitides. Treatment with immunosuppressive drugs lowered the risk of visual loss. A relapsing course suggested an increased risk for visual loss but was not statistically significant, perhaps owing to low numbers of recurrences.

ULTRA-WIDE-FIELD FUNDUS AUTOFLUORESCENCE FINDINGS IN PATIENTS WITH ACUTE ZONAL OCCULT OUTER RETINOPATHY.

PURPOSE: To determine whether ultra-wide-field fundus autofluorescence (UWFFAF) findings in acute zonal occult outer retinopathy correlated well with perimetry, optical coherence tomography, and electroretinography findings. METHODS: Retrospective observational study on 16 eyes of 10 subjects with AZOOR seen at a single referral center from October 2012 to March 2015 who had UWFFAF performed. Chi-square analysis was performed to compare categorical variables, and Mann-Whitney U test used for comparisons of nonparametric continuous variables. RESULTS: All eyes examined within 3 months of symptom onset (five of the five eyes) had diffusely hyperautofluorescent areas on UWFFAF. The remaining eyes contained hypoautofluorescent lesions with hyperautofluorescent borders. In 11/16 (68.8%) eyes, UWFFAF showed the full extent of lesions that would not have been possible with standard fundus autofluorescence centered on the fovea. There were 3 patterns of spread: centrifugal spread (7/16, 43.8%), centripetal spread (5/16, 31.3%), and centrifugal + centripetal spread (4/16, 25.0%). The UWFFAF lesions corresponded well with perimetric, optical coherence tomography, and electroretinography abnormalities. CONCLUSION: The UWFFAF along with optical coherence tomography can be useful in the evaluation and monitoring of acute zonal occult outer retinopathy patients.

Evaluating Efficacy of Aflibercept in Refractory Exudative Age-Related Macular Degeneration With OCT Segmentation Volumetric Analysis.

BACKGROUND AND OBJECTIVE: To use automated segmentation software to analyze spectral-domain optical coherence tomography (SD-OCT) scans and evaluate the effectiveness of aflibercept (Eylea; Regeneron, Tarrytown, NY) in the treatment of patients with exudative age-related macular degeneration (AMD) refractory to other treatments. PATIENTS AND METHODS: Retrospective chart review of 16 patients refractory to bevacizumab (Avastin; Genentech, South San Francisco, CA)/ranibizumab (Lucentis; Genentech, San Francisco, CA) treatment was conducted. Visual acuity, central foveal thickness (CFT), maximum fluid height, pigment epithelial detachment (PED) volume, sub-retinal fluid (SRF) volume, fluid-free time interval, and adverse effects were evaluated. Automated segmentation analysis was used to quantify improvement. RESULTS: With aflibercept treatment, there was a statistically significant improvement in visual acuity by 1 line (P = .020), in CFT by 74.02 µm (P = .001), and in maximum fluid height by 31.9 µm (P= .011). Total PED and SRF volume also decreased significantly by 1.50 µm(3) × 10(8) µm(3) (P = .013). Anatomic improvement was confirmed by automated segmentation analysis. CONCLUSION: This study demonstrates utility of automated segmentation software in quantifying anatomic improvement with aflibercept treatment in exudative AMD refractory to other anti-vascular endothelial growth factor treatments.

Profiling of Cytokines Secreted by Conventional Aqueous Outflow Pathway Endothelial Cells Activated In Vitro and Ex Vivo With Laser Irradiation.

PURPOSE: To profile which cytokine genes are differentially expressed (DE) as up- or downregulated by cultured human trabecular meshwork (TMEs) and Schlemm's canal endothelial cells (SCEs) after three experimental treatments consisting of selective laser trabeculoplasty (SLT) irradiation, exposure to media conditioned either by SLT-irradiated TMEs (TME-cm) or by SCEs (SCE-cm). Also, to profile which cytokines are upregulated ex vivo in SLT-irradiated human conventional aqueous outflow pathway (CAOP) tissues. METHODS: After each treatment, Affymetrix microarray assays were used to detect upregulated and downregulated genes for cytokines and their receptors in TMEs and SCEs. ELISA and protein antibody arrays were used to detect upregulated cytokines secreted in SLT-irradiated CAOP tissues ex vivo. RESULTS: The SLT irradiation upregulated numerous cytokine genes in TMEs, but only a few in SCEs. Exposure to TME- and SCE-cm induced SCEs to upregulate many more cytokine genes than TMEs. Selective laser trabeculoplasty irradiation and exposure to TME-cm downregulated several cytokine genes in TMEs but none in SCEs. Selective laser trabeculoplasty irradiation induced one upregulated and three downregulated cytokine-receptor genes in TMEs but none in SCEs. Exposure to TME-cm induced upregulation of one and downregulation of another receptor gene in TMEs, whereas two unique cytokine-receptor genes were upregulated in SCEs. Cytokine protein expression analysis showed that at least eight cytokines were upregulated in SLT-irradiated human CAOP tissues in situ/ex vivo. CONCLUSIONS: This study has helped us identify a cytokine signaling pathway and to consider newly identified mechanisms regulating aqueous outflow that may lay the foundation for the future development of cytokine-based glaucoma therapies.

Early-Onset X-Linked Retinitis Pigmentosa in a Heterozygous Female Harboring an Intronic Donor Splice Site Mutation in the Retinitis Pigmentosa GTPase Regulator Gene.

PURPOSE: To report a heterozygous female presenting with an early-onset and severe form of X-linked retinitis pigmentosa (XLRP). PATIENTS AND METHODS: This is a case series presenting the clinical findings in a heterozygous female with XLRP and two of her family members. Fundus photography, fundus autofluorescence, ocular coherence tomography, and visual perimetry are presented. RESULTS: The proband reported here is a heterozygous female who presented at the age of 8 years with an early onset and aggressive form of XLRP. The patient belongs to a four-generation family with a total of three affected females and four affected males. The patient was initially diagnosed with retinitis pigmentosa (RP) at the age of 4 years. Genetic testing identified a heterozygous donor splice site mutation in intron 1 (IVS1 + 1G > A) of the retinitis pigmentosa GTPase regulator gene. The father of the proband was diagnosed with RP when he was a young child. The sister of the proband, evaluated at the age of 6 years, showed macular pigmentary changes. CONCLUSIONS: Although carriers of XLRP are usually asymptomatic or have a mild disease of late onset, the proband presented here exhibited an early-onset, aggressive form of the disease. It is not clear why some carrier females manifest a severe phenotype. A better understanding of the genetic processes involved in the penetrance and expressivity of XLRP in heterozygous females could assist in providing the appropriate counseling to affected families.

Probable Association of an Attack of Bilateral Acute Angle-Closure Glaucoma With Duloxetine.

OBJECTIVE: To report a patient who had an attack of bilateral acute angle-closure glaucoma (ACG) probably associated with the use of duloxetine. CASE SUMMARY: The case reported here involves an 81-year-old Caucasian woman whose past ocular history was unremarkable except for high hyperopia and cataract. The patient developed ocular symptoms 2 days after starting duloxetine, a serotonin norepinephrine reuptake inhibitor (SNRI) and was diagnosed with acute ACG. The elevated intraocular pressure (IOP) was successfully lowered with medical treatment, and the patient was advised to discontinue duloxetine. She subsequently underwent laser iridotomy in both eyes, and her IOP remained adequately controlled. A score of 6 was obtained using the Naranjo adverse drug reaction probability scale, suggesting duloxetine as the probable cause of the attack of ACG in this patient. DISCUSSION: There are a few previous reports of acute ACG associated with venlafaxine, another member of the class of SNRIs. In addition, there are several reports of ACG associated with members of the related class of selective serotonin reuptake inhibitors (SSRIs)-namely, fluoxetine, paroxetine, fluvoxamine, sertraline, citalopram, and escitalopram. The mechanism responsible for the precipitation of ACG by members of these 2 classes of drugs is likely a result of mydriasis caused by their adrenergic effects, weak anticholinergic activities, or the increased levels of serotonin. CONCLUSION: Because the SNRIs, including duloxetine, and SSRIs are commonly used in the management of depression or chronic pain, caution is warranted with the use of these drugs in patients with risk factors for ACG.