Ophthalmology procedure trends in the United States during the COVID-19 pandemic.

PURPOSE: To evaluate the relationship between the COVID-19 pandemic and ophthalmic procedural volume. METHODS: A retrospective cohort study using TriNetX, a federated electronic health record's research network was done. Monthly Current Procedural Terminology-specific volumes per healthcare organization were clustered chronologically to calculate average volumes into 3-month seasons to calculate average procedural volumes. An aggregate of the total pandemic period (March 2020-August 2021) was compared to corresponding figures in pre-pandemic timeframes. RESULTS: Intravitreal injections were the most prevalent procedure in this time period with 320,106 occurrences. Phacoemulsification cataract surgery was the second most prevalent (N = 176,095) procedure. From March 2020 to August 2021, a mean pandemic volume of 266.7 (SD = 15) was observed, a 5% decrease (p < 0.05) in procedures compared to the pre-pandemic mean of 280.8 (SD = 26.1). Spring 2020 exhibited the sharpest seasonal decrease in procedural volume (- 88%). The largest count of statistically significant increases in procedure volume was in Spring 2021 (+ 18%). The aggregate mean volume per HCO showed significant decreases for 11 out of 17 procedures in the 12 month March 2020-February 2021 timeframe and significant decreases for 10 out of 17 procedures over the 18-month March 2020-August 2021 pandemic period. CONCLUSIONS: This study highlights the relative inverse relationship between COVID-19 cases and ophthalmic procedure volume in America. Quantifying ophthalmic procedure trends is important in retrospectively assessing surgical disruptions and prospectively accommodating delayed surgeries. Furthermore, awareness of these trends could help ophthalmologists prepare should similar disruptions occur in the setting of future pandemics or national disasters.

Retinal vasculitis with Chronic Recurrent Multifocal Osteomyelitis: a case report and review of the literature.

BACKGROUND: Concurrent presentation of retinal vasculitis with mixed sclerotic and lytic bone lesions is rare. CASE PRESENTATION: We present the case of a 37-year old woman with a several year history of episodic sternoclavicular pain who presented for rheumatologic evaluation due to a recent diagnosis of retinal vasculitis. We review the differential diagnosis of retinal vasculitis, along with the differential diagnosis of mixed sclerotic and lytic bone lesions. Ultimately, bone marrow biopsy confirmed diagnosis of chronic recurrent multifocal osteomyelitis (CRMO). Concurrent presentation of CRMO with retinal vasculitis is extremely rare but important to recognize. The patient demonstrated clinical response to prednisone and tumor necrosis factor-alpha inhibition (TNF-i). CONCLUSION: This case reports and unusual presentation of CRMO spectrum disease involving the sternum and sternoclavicular joint with concurrent retinal vasculitis.

Consensus on the Diagnosis and Management of Nonparaneoplastic Autoimmune Retinopathy Using a Modified Delphi Approach.

PURPOSE: To develop diagnostic criteria for nonparaneoplastic autoimmune retinopathy (AIR) through expert panel consensus and to examine treatment patterns among clinical experts. DESIGN: Modified Delphi process. METHODS: A survey of uveitis specialists in the American Uveitis Society, a face-to-face meeting (AIR Workshop) held at the National Eye Institute, and 2 iterations of expert panel surveys were used in a modified Delphi process. The expert panel consisted of 17 experts, including uveitis specialists and researchers with expertise in antiretinal antibody detection. Supermajority consensus was used and defined as 75% of experts in agreement. RESULTS: There was unanimous agreement among experts regarding the categorization of autoimmune retinopathies as nonparaneoplastic and paraneoplastic, including cancer-associated retinopathy and melanoma-associated retinopathy. Diagnostic criteria and tests essential to the diagnosis of nonparaneoplastic AIR and multiple supportive criteria reached consensus. For treatment, experts agreed that corticosteroids and conventional immunosuppressives should be used (prescribed) as first- or second-line treatments, though a consensus agreed that biologics and intravenous immunoglobulin were considered appropriate in the treatment of nonparaneoplastic AIR patients regardless of the stage of disease. Experts agreed that more evidence is needed to treat nonparaneoplastic AIR patients with long-term immunomodulatory therapy and that there is enough equipoise to justify randomized, placebo-controlled trials to determine if nonparaneoplastic AIR patients should be treated with long-term immunomodulatory therapy. Regarding antiretinal antibody detection, consensus agreed that a standardized assay system is needed to detect serum antiretinal antibodies. Consensus agreed that an ideal assay should have a 2-tier design and that Western blot and immunohistochemistry should be the methods used to identify antiretinal antibodies. CONCLUSIONS: Consensus was achieved using a modified Delphi process to develop diagnostic criteria for nonparaneoplastic AIR. There is enough equipoise to justify randomized, placebo-controlled trials to determine whether patients with nonparaneoplastic AIR should be treated with long-term immunomodulatory therapy. Efforts to develop a standardized 2-tier assay system for the detection of antiretinal antibodies have been initiated as a result of this study.

Subconjunctival sirolimus in the treatment of autoimmune non-necrotizing anterior scleritis: results of a phase I/II clinical trial.

PURPOSE: To investigate the safety, tolerability and efficacy of subconjunctival sirolimus injections as a treatment for active, autoimmune, non-necrotizing anterior scleritis. DESIGN: Phase I/II, single-center, open-label, nonrandomized, prospective pilot study. METHODS: Five participants with active, autoimmune, non-necrotizing anterior scleritis with scleral inflammatory grade of ≥1+ in at least 1 quadrant with a history of flares were enrolled. A baseline injection was given, with the primary outcome measure of at least a 2-step reduction or reduction to grade zero in the study eye by 8 weeks. Secondary outcomes included changes in visual acuity and intraocular pressure, ability to taper concomitant immunosuppressive regimen, and number of participants who experienced a disease flare requiring reinjection. Safety outcomes included the number and severity of systemic and ocular toxicities, and vision loss ≥15 ETDRS letters. The study included 6 visits over 4 months with an extension phase to 1 year for participants who met the primary outcome. RESULTS: All participants (N = 5, 100%; 95% CI [0.60, 1.00]) met the primary outcome in the study eye by the week 8 visit. There was no significant change in mean visual acuity or intraocular pressure. Three out of 5 patients (60%) experienced flares requiring reinjection. No systemic toxicities were observed. Two participants (40%) experienced a localized sterile inflammatory reaction at the site of the injection, which resolved without complication. CONCLUSIONS: Subconjunctival sirolimus leads to a short-term reduction in scleral inflammation, though relapses requiring reinjection do occur. There were no serious adverse events, though a local sterile conjunctival inflammatory reaction was observed.

Diagnostic procedures in vitreoretinal lymphoma.

PURPOSE: To evaluate the type and number of diagnostic interventions needed to confirm the presence of vitreoretinal lymphoma. METHOD: Chart review of interventions performed for diagnosis of vitreoretinal lymphoma. RESULTS: Of the 27 cases, diagnosis was made by pars plana vitrectomy in 13 (48.1%), vitreous tap in 2 (7.4%), anterior chamber tap in 1 (3.7%), chorioretinal biopsy in 2 (7.4%), brain biopsy in 5 (18.5%), and cerebrospinal fluid cytology via lumbar puncture in 4 (14.8%). Ten (37%) had definitive results on the first procedure, and 17 (63%) had at least one false negative. Vitrectomy was the most common procedure performed. Patients required a mean of 2.1 procedures. Average time from onset of symptoms to confirmed histopathologic diagnosis was 13.9 months. CONCLUSION: Vitreoretinal lymphoma is difficult to recognize and requires a high degree of clinical suspicion. It often takes more than one invasive procedure to make the diagnosis.

Comparison of wide-field fluorescein angiography and 9-field montage angiography in uveitis.

PURPOSE: To compare qualitatively and quantitatively Optos fundus camera fluorescein angiographic images of retinal vascular leakage with 9-field montage Topcon fluorescein angiography (FA) images in patients with uveitis. We hypothesized that Optos images reveal more leakage in patients with uveitis. DESIGN: Retrospective, observational case series. METHODS: Images of all patients with uveitis imaged with same-sitting Optos FA and 9-field montage FA during a 9-month period at a single institution (52 eyes of 31 patients) were graded for the total area of retinal vascular leakage. The main outcome measure was area of fluorescein leakage. RESULTS: The area of apparent FA leakage was greater in Optos images than in 9-field montage images (median 22.5 mm(2) vs 4.8 mm(2), P < 0.0001). Of the 49 (45%) eyes with gradable photos, 22 had at least 25% more leakage in the Optos image than in the montage image; 2 (4.1%) had at least 25% less leakage in Optos; and 25 (51%) were similar in the 2 modalities. There were 2 eyes that had no apparent retinal vascular leakage in 9-field montage but were found to have apparent leakage in Optos images. Of the 49 eyes, 23 had posterior pole leakage, and of these, 17 (73.9%) showed more posterior pole leakage in the Optos image. A single 200-degree Optos FA image captured a mean 1.50× the area captured by montage photography. CONCLUSIONS: More retinal vascular pathology, in both the periphery and the posterior pole, is seen with Optos FA in patients with uveitis when compared with 9-field montage. The clinical implications of Optos FA findings have yet to be determined.

Neoplastic masquerade syndromes in patients with uveitis.

PURPOSE: To identify the demographic and clinical characteristics, along with the frequency, of neoplastic masquerade syndromes in a tertiary uveitis clinic. DESIGN: A retrospective observational cohort. METHODS: Demographic and clinical data on all patients presenting to the National Eye Institute (NEI) with uveitis between 2004 and 2012 were used to compare neoplastic masquerade syndromes and uveitis. RESULTS: A total of 853 patients presenting with uveitis were identified. Of these, 21 (2.5%) were diagnosed with neoplastic masquerade syndromes. The average age at presentation of masquerade syndrome patients was 57 years (median, 55; range, 38-78); for uveitis, 42 years (median, 43; range, 3-98) (P = 0.0003). There were 48% females in the masquerade syndromes group, compared with 59% females in the uveitis group. African American patients represented 9% of the masquerade syndrome patients and 36% of uveitis patients (P = 0.01). Mean worse eye visual acuity was 0.89 (20/160) in neoplastic masquerade syndromes, and 0.66 (20/100) in the uveitis group (P = 0.21). Of masquerade syndrome patients, 90% had posterior inflammation, compared with 63% of uveitis patients (P = 0.006). Of those with masquerade syndromes, 48% of patients had unilateral disease, compared with 27% of the uveitis patients (P = 0.04). CONCLUSIONS: Patients with neoplastic masquerade syndromes were more likely to be older, male, or non-African American and to have posterior segment inflammation and unilateral disease. Patients with masquerade syndromes also had worse visual acuity than did uveitis patients. These differences in clinical characteristics may help to raise the suspicion for neoplastic masquerade syndromes.

Autoimmune retinopathy.

PURPOSE: To provide a detailed review of current clinical guidelines for the diagnosis, work-up and treatment of autoimmune retinopathy and to preview briefly possible future therapies. DESIGN: Perspective based on literature review and clinical expertise. METHODS: Interpretation of current literature, relying on the authors' clinical experience. RESULTS: Autoimmune retinopathy is a rare immunologic disease characterized by the presence of circulating antiretinal antibodies along with electroretinographic and visual field abnormalities. An ophthalmic examination can be normal or show minimal findings. The diagnosis of autoimmune retinopathy is made difficult by diagnostic criteria that are both limited and nonstandardized. Currently, the diagnosis is made based on the demonstration of serum antiretinal antibodies and the presence of clinical manifestations (including abnormal electroretinographic findings). The mere presence of these antibodies is not diagnostic. Lack of an accepted gold standard for antiretinal antibodies detection and poor interlaboratory concordance make the diagnosis challenging. There are anecdotal reports of immunosuppressive therapy in autoimmune retinopathy; however, the response to treatment is variable, with more favorable results achieved in paraneoplastic retinopathy, particularly cancer-associated retinopathy, with a combination of chemotherapy and immunosuppression. Whether an earlier attempt to treat nonparaneoplastic autoimmune retinopathy would be more beneficial is unknown. Early treatment attempts are limited by lack of sensitive and specific assays and definitive clinical criteria. CONCLUSIONS: Little is known about the clinical course, prognosis and treatment of autoimmune retinopathy. Additional studies should examine the specificity and pathogenicity of antiretinal antibodies and screen for biomarkers, and they should be conducted concurrently with studies seeking to identify appropriate treatment.

Diagnosis of occult melanoma using transient receptor potential melastatin 1 (TRPM1) autoantibody testing: a novel approach.

PURPOSE: To report the first case of melanoma-associated retinopathy (MAR) and underlying occult melanoma diagnosed based on the presence of serum transient receptor potential melastatin 1 (TRPM1) autoantibodies. DESIGN: Interventional case report with basic science correlation. PARTICIPANTS: One patient with MAR. INTERVENTION: Testing for the presence of serum TRPM1 autoantibodies. MAIN OUTCOME MEASURES: Diagnosis of an occult melanoma involving the axillary lymph nodes (unknown primary site) and MAR based on the presence of TRPM1 autoantibodies in the patient's serum. RESULTS: The patient's clinical exam was remarkable for mild intraocular inflammation in both eyes and retinal hemorrhages with an apparent choroidal neovascularization in the left eye, which was confirmed by fluorescein angiography and indocyanine green angiography testing. Humphrey visual field 30-2 SITA-fast (Humphrey Visual Field Analyzer, Carl Zeiss Meditec, Inc, Dublin, CA) demonstrated diffuse depression in both eyes out of proportion to the clinical exams, prompting electroretinography testing that revealed an electronegative response. Dark-adapted thresholds were markedly elevated and mediated by cones. Due to concern for MAR, a systemic work-up for melanoma was performed by the primary care physician that was unrevealing. Given our continued clinical suspicion for MAR, the patient's serum was sent for evaluation for TRPM1 autoantibodies. The patient's serum applied to normal human retina exhibited positivity in the inner nuclear layer. Application of the patient's serum to wild-type and TRPM1 knockout mouse retina revealed strongly labeled bipolar cells in the wild-type retina, but not in the TRPM1 knockout retina, indicating TRPM1-dependent immunoreactivity. The antigen was confirmed as TRPM1 by labeling of TRPM1-transfected human embryonic kidney 293 cells. Additional systemic work-up prompted by this finding resulted in identification of an occult metastatic melanoma involving the axillary lymph nodes with an unknown primary site. The patient underwent surgical excision of the occult melanoma without evidence of other sites of metastases. He also received intravenous immunoglobulin therapy and his vision has stabilized. CONCLUSIONS: This is the first reported case of a melanoma-associated retinopathy diagnosed utilizing the innovative approach of testing for serum TRPM1 autoantibodies.

Subconjunctival Palomid 529 in the treatment of neovascular age-related macular degeneration.

BACKGROUND: Recent evidence suggests that neovascular age-related macular degeneration (AMD) may have an immune mediated component. Palomid 529, an investigational medication involving the immune Akt/mTOR pathway, is unique in dissociating both targets of rapamycin complexes TORC1 and TORC2. This small short-term pilot study assesses the safety of subconjunctival Palomid 529 in the treatment of neovascular AMD, with some limited efficacy information. METHODS: In this 12-week phase I open-label prospective pilot study, five participants with neovascular age-related macular degeneration that were refractory to intravitreal anti-vascular endothelial growth factor (VEGF) received three serial monthly subconjunctival doses of 1.9 mg Palomid 529. All participants were also offered concomitant monthly intravitreal anti-VEGF injections. Safety was monitored via adverse events recording. Additional outcome measures included visual acuity, optical coherence tomography, fluorescein angiography, indocyanine green angiography and fundus photography. RESULTS: The study drug was well-tolerated by all participants. There were no drug-related adverse events and no serious adverse events. A depot formed at the injection site, which persisted at the end of the study. In these anti-VEGF refractory patients, no clinically important changes in best-corrected visual acuity, fluorescein leakage pattern, choroidal neovascularization size on indocyanine green angiography, or autofluorescence pattern on fundus autofluorescence were observed compared to baseline. The fluid status, assessed with optical coherence tomography showed that central retinal thickness and macular volume remained stable in three participants, while the other two participants clinically progressed. CONCLUSIONS: Serial subconjunctival injections of Palomid 529 were well-tolerated and resulted in depot formation. There were no concerns for any ocular or systemic toxicity during this small short-term study. Larger randomized studies are required to determine efficacy.

Secondary intraocular uveal involvement by primary paranasal sinus lymphoma.

To report an unusual case of primary paranasal sinus lymphoma associated with intraocular secondary uveal involvement. Retrospective case report emphasizing the histopathologic diagnosis as well as imaging studies, and review of the pertinent literature. The diagnosis of ophthalmologic lymphoma can be difficult due to the infrequency of the disease, the diverse presentation, and the need for biopsy for definitive diagnosis. Prior clinical history and systemic testing may be important confirmations in diagnosing such cases.

Bullous variant of acral erythema due to methotrexate.

Chemotherapy-induced acral erythema is a painful erythema of the palms and soles which occurs following chemotherapy. It is usually seen due to cytarabine, doxorubicin and fluorouracil. We present a 40-year-old male patient, a biopsy proven case of squamous cell carcinoma of the floor of the mouth, who developed a bullous variant of acral erythema after a single intravenous dose of methotrexate. He also had fever, buccal mucositis, leucopenia, thrombocytopenia and hyperpigmented macular rash on the face and upper trunk. The bullous variant of acral erythema due to methotrexate has rarely been reported.

Neurological manifestations of Hansen's disease and their management.

Hansen's disease is almost eliminated from developed countries but in developing countries of Africa, Asia and Latin America leprosy is still considered to be a public health problem. Mycobacterium leprae have the affinity for peripheral nerves and neuropathy is a cardinal manifestation of the disease. The nerve damage affects sensory, motor, and autonomic fibers resulting in the physical impairments and limitation of physical activities and social participation. Leprosy is a curable disease and treatment provided in the early stages will avert the disabilities. Approach to the neuritic leprosy depends on its clinical characteristics, nerve biopsy, and histological appearance of dermatological and neurological lesions. In this article we review the literature and discuss the pathology, clinical features, diagnosis and management of neurological manifestations of leprosy.

Ulnar nerve abscess and relapse in a patient with indeterminate leprosy 1 year after completion of multidrug therapy.

The introduction of multidrug therapy has efficiently controlled leprosy in developing countries. However, Mycobacterium laprae may survive and cause relapse despite adequate treatment with antileprosy drugs. Relapse may be characterized by a combination of new signs or symptoms and presence of acid-fast bacilli on skin or nerve biopsy samples. We report a case of a child in whom ulnar abscess developed 12 months after successful completion of multidrug therapy with clinical and histopathological evidence of relapse.

CLAVATA1 dominant-negative alleles reveal functional overlap between multiple receptor kinases that regulate meristem and organ development.

The CLAVATA1 (CLV1) receptor kinase controls stem cell number and differentiation at the Arabidopsis shoot and flower meristems. Other components of the CLV1 signaling pathway include the secreted putative ligand CLV3 and the receptor-like protein CLV2. We report evidence indicating that all intermediate and strong clv1 alleles are dominant negative and likely interfere with the activity of unknown receptor kinase(s) that have functional overlap with CLV1. clv1 dominant-negative alleles show major differences from dominant-negative alleles characterized to date in animal receptor kinase signaling systems, including the lack of a dominant-negative effect of kinase domain truncation and the ability of missense mutations in the extracellular domain to act in a dominant-negative manner. We analyzed chimeric receptor kinases by fusing CLV1 and BRASSINOSTEROID INSENSITIVE1 (BRI1) coding sequences and expressing these in clv1 null backgrounds. Constructs containing the CLV1 extracellular domain and the BRI1 kinase domain were strongly dominant negative in the regulation of meristem development. Furthermore, we show that CLV1 expressed within the pedicel can partially replace the function of the ERECTA receptor kinase. We propose the presence of multiple receptors that regulate meristem development in a functionally related manner whose interactions are driven by the extracellular domains and whose activation requires the kinase domain.