Treatment outcomes of macular holes in the setting of uveitis: a scoping review.

OBJECTIVE: We conducted a systematic review to evaluate the outcome of macular hole (MH) treatment in eyes with uveitis. DATA SOURCE: We searched PubMed and Embase databases from inception through August 15, 2021. STUDY SELECTION: We included eyes with MHs secondary to uveitis that were managed medically or underwent pars plana vitrectomy (PPV). We excluded eyes with idiopathic MH and those secondary to causes other than uveitis. RESULTS: Of 27 articles, we identified 86 eyes with MH secondary to uveitis that received either conservative medical treatment alone or PPV with adequate follow-up. The mean (± SD) age of patients included in this review was 46.6 (± 16.8) years; 60.5% were males. The most common etiology of uveitis was Behçet's disease (34.6%) and toxoplasmosis (19.7%). The most common anatomical location of uveitis was posterior (59.3%) followed by panuveitis (35.2%). The mean (± SD) baseline LogMAR vision was 1.1 (± 0.5). Conservative medical treatment was employed in 34.9%, while PPV was performed in 65.1% of eyes. Overall, the mean (SD) LogMAR vision improved from 1.1 (± 0.5) at baseline to 0.7 (± 0.5) after treatment. Inflammation-related MHs were closed in 40% of eyes after conservative therapy and in 87.5% of eyes after PPV. Visual improvement occurred in most eyes (83.9%) that had successful closure of their MH. CONCLUSIONS: Visual improvement occurs in most eyes that had successful closure of their inflammation-related MH. Conservative medical control of uveitis may lead to closure of inflammation-related MHs and is an important step prior to surgery, if required. Surgical intervention for inflammation-related MHs is associated with good functional and anatomical results.

SUPRACHOROIDAL INJECTION OF TRIAMCINOLONE ACETONIDE, CLS-TA, FOR MACULAR EDEMA DUE TO NONINFECTIOUS UVEITIS: A Randomized, Phase 2 Study (DOGWOOD).

PURPOSE: Evaluate a single suprachoroidal injection of a proprietary triamcinolone acetonide suspension, CLS-TA, in subjects with macular edema due to noninfectious uveitis. METHODS: Randomized, controlled, masked Phase 2 study. Safety and efficacy of a single suprachoroidal injection of CLS-TA (4.0 and 0.8 mg in a 4:1 ratio) were assessed at 1 and 2 months after injection. The primary efficacy endpoint was change in central subfield thickness from baseline to Month 2, assessed by spectral domain optical coherence tomography. RESULTS: Twenty-two adults were enrolled. The primary endpoint was met in subjects who received suprachoroidal injection of CLS-TA 4.0 mg, mean central subfield thickness significantly decreased from baseline by 135 µm and 164 µm at Month 1 (P = 0.0056) and Month 2 (P = 0.0017), respectively. At Month 2, 69% of subjects who received 4.0 mg experienced ≥20% reduction in central subfield thickness, and 65% had improvement of best-corrected visual acuity of ≥5 Early Treatment Diabetic Retinopathy Study letters, with a mean improvement of 9.2 letters (P = 0.0004). Safety analyses supported acceptable safety/tolerability, with no corticosteroid-related increases in intraocular pressure. CONCLUSION: A single suprachoroidal injection of CLS-TA (4.0 mg; 0.1 mL) in subjects with macular edema due to noninfectious uveitis was well-tolerated, significantly reduced central subfield thickness from baseline at 2 months, and significantly improved visual acuity.

VISCOELASTIC ASSISTED DRAINAGE OF SUPRACHOROIDAL HEMORRHAGE ASSOCIATED WITH SETON DEVICE IN GLAUCOMA FILTERING SURGERY.

PURPOSE: The purpose of this article is to describe a novel surgical technique for the management of large suprachoroidal hemorrhages associated with the insertion of glaucoma seton devices. METHODS: In this interventional case series, the authors describe six eyes of six patients who had management of suprachoroidal hemorrhage with pars plana choroidal drainage along with simultaneous insertion of viscoelastic into the posterior segment. All patients had a median of 8-month postoperative follow-up. RESULTS: Five of the 6 patients had useful final vision ranging from 20/40 to 20/200. In all cases, the postoperative intraocular pressures did not increase beyond 28 mmHg and responded to aqueous humor suppressants. CONCLUSION: As suprachoroidal hemorrhage can be a devastating complication of glaucoma surgery, the authors report a relatively straightforward surgical technique that can restore ambulatory vision in a high proportion of patients.

Sight-threatening ocular manifestations of acute febrile neutrophilic dermatosis (Sweet's syndrome).

Sweet's syndrome is a primarily dermatologic disorder with many features of systemic inflammation. It is generally characterized by a neutrophilic dermatosis in the setting of fever and an elevated white blood cell count. Inflammation has been described to occur in many organ systems including the lung, bone, liver, spleen, brain and eye. Ocular inflammation is a well-known comorbidity that may occur in the setting of Sweet's syndrome, including conjunctivitis, episcleritis, scleritis, iritis and choroiditis, among other forms. In the current article, we have compiled a series of cases that describe three separate patients who demonstrated a rare form of ocular involvement in Sweet's syndrome, retinal vasculitis. The evidence from these three cases and other reports in recent ophthalmologic literature suggest overlapping of ocular manifestations of Sweet's syndrome and the closely related Behçet's disease. It is important to be aware of the sometimes challenging differential between these two disorders and their sight-threatening complications.

Application of Ophthalmic Electrophysiology in Inflammatory Disorders of Retina and Optic Nerve.

This review covers the utility of electrophysiological studies relevant to inflammatory diseases of the retina in conditions such as acute posterior multifocal placoid pigment epitheliopathy, acute zonal occult outer retinopathy, Adamantiades-Behçet disease, autoimmune retinopathy and neuro-retinopathy, birdshot chorioretinopathy, multiple evanescent white dot syndrome, and Vogt-Koyanagi-Harada disease. Electrophysiological studies can help with the diagnosis, prognostication, evaluation of treatment effects, and follow-up for these conditions.

Tattoo-Induced Exacerbations of Systemic Disease and Uveitis.

Purpose: To examine an underreported and underdiagnosed phenomenon with implications for the pathophysiological mechanisms of tattoo-induced uveitis. Methods: Two cases highlighting the clinical presentation of tattoo-related uveitis were evaluated. Results: A 28-year-old man with biopsy-proven sarcoidosis and ocular manifestations presented with worsening retinal vasculitis after acquiring a red-ink tattoo. Each subsequent flare followed acquisition of a new tattoo. A 31-year-old woman without systemic sarcoidosis presented with multiple episodes of bilateral intermediate uveitis and macular edema concurrent with inflammatory granulomas to recently acquired black-ink tattoos. A skin biopsy in both patients showed cutaneous noncaseating granulomas. Conclusions: These cases add to those reported in the literature and emphasize the importance of understanding the modifiable factors of inflammatory ocular disease. Future study is necessary to understand the mechanisms of tattoo-related uveitis.

Updates on Functional and Morphologic Features via State-of-the-Art Testing in Some Clinically Evident Ocular Diseases.

Recent research on functional and morphologic features is relevant to the diagnosis of ocular diseases [...].

Suggestive association between PLA2G12A single nucleotide polymorphism rs2285714 and response to anti-vascular endothelial growth factor therapy in patients with exudative age-related macular degeneration.

PURPOSE: The use of anti-vascular endothelial growth factor (anti-VEGF) therapy, with drugs such as ranibizumab and bevacizumab, to treat neovascular age-related macular degeneration (nAMD) produces an effective but widely variable response. Identifying markers that predict differentiated response could serve as a valuable assay in developing more personalized medicine. This study aimed to identify single nucleotide polymorphisms (SNPs) that influence the outcome of treatment with anti-VEGF therapy for AMD. METHODS: One hundred six patients with nAMD were treated with either ranibizumab or bevacizumab as needed over a period of 12 months. Visual acuity and the presence of macular fluid were measured with optical coherence tomography at baseline, six months, and 12 months. Patients were then classified as good or poor responders based on change in visual acuity and macular fluid on follow-up visits. DNA extracted from blood was genotyped with a TaqMan-based allelic discrimination SNP assay for 21 SNPs in six candidate genes (PLAG12A, IL23R, STAT3, VEGFA, KDR, and HIF1A). The SNPs were primarily selected based on previously reported associations with AMD and functional involvement in angiogenesis pathways. SNPs shown to be promising for association with anti-VEGF therapy were then assessed in an independent AMD case-control cohort. RESULTS: Of the 106 patients with nAMD, 77 were classified as good responders and 29 as poor responders. For rs2285714 (PLA2G12A), the frequency of minor allele T was 40.1% for good responders compared to 51.7% for poor responders (odds ratio: 1.60, 95% confidence interval of odds ratio: 0.87-2.94, p=0.13). Genetic model analysis of rs2285714 (PLA2G12A) demonstrated an association between rs2285714 (PLA2G12A) and therapy response in a dominant genotypic model. Patients carrying at least one T allele of rs2285714 were 2.79 times (95% confidence interval=1.02-7.69, p<0.05) more likely to be poor responders (79.3% of poor responders) than good responders (57.3% of good responders). However, after adjusting for multiple testing by the false discovery rate or Bonferroni correction, the initially observed association was no longer statistically significant. No association was identified between the remaining SNPs and response status. The SNP rs2285714 of PLA2G12A was not significantly associated with AMD in an independent AMD case-control cohort. CONCLUSIONS: Data suggest a possible weak association between rs2285714 (PLA2G12A) and response to anti-VEGF therapy, but the association must be confirmed in additional cohorts with larger patient samples. Identifying factors that predict the differentiated response could provide a valuable assay for developing approaches in personalized medicine.

Low-dose methotrexate for the treatment of chronic central serous chorioretinopathy: a retrospective analysis.

PURPOSE: To evaluate the utility of oral methotrexate (MTX) for the treatment of chronic central serous chorioretinopathy (CSCR). METHODS: Retrospective review of all eyes of patients on oral MTX as treatment for chronic CSCR in three different centers. Visual acuity as well as optical coherence tomography central macular thickness and total volume parameters were analyzed. Complete blood count and serum chemistry results were monitored. RESULTS: Nine eyes of 9 patients treated with MTX for chronic CSCR met the criteria for analysis. Mean duration of CSCR was 28 months (range, 3-94 months). Mean starting dose of oral MTX was 7.04 mg (range, 5-10 mg), and mean final dose was 7.27 mg (range, 5-10 mg). The mean duration of treatment was 89 days. Mean visual acuity improved from 20/67 at baseline to 20/35 at 8 weeks (P < 0.01, paired t-test). Mean central macular thickness improved from 309 µm to 213 µm at 8 weeks (P < 0.01, paired t-test). Mean total macular volume improved from 8.14 to 7.21 at 8 weeks (P ≤ 0.02, paired t-test). Eighty-three percent of the patients achieved total resolution of subretinal fluid. No MTX-associated toxicity was evident. CONCLUSION: Methotrexate may have a role in the treatment of chronic CSCR as evidenced by these results. A randomized controlled clinical trial is warranted to better understand the effects of MTX in these patients.

Intraocular inflammation secondary to intravitreal brolucizumab treated successfully with Sub-Tenon triamcinolone: A case report.

PURPOSE: To report on a case of successful treatment of intraocular inflammation (IOI) secondary to brolucizumab intravitreal injection that responded to a single sub-Tenon injection of triamcinolone. OBSERVATIONS: An 81-year-old female with a longstanding history of exudative age-related macular degeneration (AMD) was unresponsive to various regimens of anti-VEGF injections. Her AMD was treated with one intravitreal injection of brolucizumab (6mg/0.05ml) into the right eye. On a follow-up visit, she had a new-onset conjunctival injection, with anterior chamber and vitreous inflammation, in the right eye, which was diagnosed as non-granulomatous iridocyclitis. The patient was treated with one posterior sub-Tenon injection of triamcinolone (40mg/ml) into the right eye. Subsequently, there was a durable resolution of inflammation, and her vision improved along with the resolution of her exudation. CONCLUSIONS AND IMPORTANCE: This case suggests that some brolucizumab-related IOI episodes may be treated with posterior sub-Tenon triamcinolone. Further studies may serve to elucidate the role of sub-Tenon triamcinolone in brolucizumab-associated IOI.

Use of Visual Electrophysiology to Monitor Retinal and Optic Nerve Toxicity.

It is important for clinicians to consider exposure to toxic substances and nutritional deficiencies when diagnosing and managing cases of vision loss. In these cases, physiologic damage can alter the function of key components of the visual pathway before morphologic changes can be detected by traditional imaging methods. Electrophysiologic tests can aid in the early detection of such functional changes to visual pathway components, including the retina or optic nerve. This review provides an overview of various electrophysiologic techniques, including multifocal electroretinogram (mfERG), full-field ERG (ffERG), electrooculogram (EOG), pattern electroretinogram (PERG), and visual evoked potential (VEP) in monitoring the retinal and optic nerve toxicities of alcohol, amiodarone, cefuroxime, cisplatin, deferoxamine, digoxin, ethambutol, hydroxychloroquine, isotretinoin, ocular siderosis, pentosane, PDE5 inhibitors, phenothiazines (chlorpromazine and thioridazine), quinine, tamoxifen, topiramate, vigabatrin, and vitamin A deficiency.

Reactivation of Acute Retinal Necrosis following SARS-CoV-2 Infection.

PURPOSE: To report on a case of reactivation of acute retinal necrosis following SARS-CoV-2 infection. METHODS: Observational case report. Observations. A 32-year-old female with a distant history of left retinal detachment secondary to necrotizing herpetic retinitis complained of right-eye vision loss, pain, redness, and photophobia. An ophthalmological examination revealed findings consistent with acute retinal necrosis of the right eye. A polymerase chain reaction (PCR) analysis of the right vitreous was positive for herpes simplex virus type 2 (HSV-2). A coronavirus disease 2019 (COVID-19) screening test using reverse transcriptase- (RT-) PCR was positive for SARS-CoV-2 RNA. CONCLUSIONS: Our case suggests that COVID-19 may cause a latent HSV infection to reactivate, causing contralateral involvement in patients with a prior history of HSV-associated acute retinal necrosis.

Ophthalmic Manifestations of Hodgkin Lymphoma: A Review.

BACKGROUND: Hodgkin lymphoma (HL) is a hematopoietic neoplasm characterized by cancerous Reed-Sternberg cells. In contrast to ophthalmic manifestations by non-HL that are well recognized, there is paucity of the literature as it relates to ophthalmic manifestation by HL. We performed a comprehensive review of published studies (case reports and small case series) to characterize the ophthalmic manifestations of HL. SUMMARY: Thirty patients were identified with ophthalmic manifestation of HL. Thirteen (43%) were male, and 14 (46%) were female (in 3 cases, sex was not specified). The median age at ophthalmic presentation was 27 years. Diagnosis of HL was made after ophthalmic manifestation in 10 (33%) cases, whereas 11 (36%) cases had a prior diagnosis of HL. Ophthalmic manifestations can be classified into 3 main groups; direct infiltration, inflammatory reaction, and paraneoplastic process. Seven cases had infiltration of the optic nerve. Uveal inflammatory reaction was reported in 21 cases. The presence of intraocular Reed-Sternberg cells had been confirmed in 1 case with granulomatous uveitis. Conjunctival and corneal reaction was seen in 3 cases. HL was in stage 2 or higher, with only 1 case with stage 1A (12 cases HL stage not specified). Seven cases (22%) died of HD, all were diagnosed with advanced lymphoma, and none was treated with chemotherapy. KEY MESSAGE: Ocular involvement in HL is extremely rare. A few cases of histopathologically confirmed optic nerve/tract infiltration are within the spectrum of CNS involvement by HL. Inflammatory uveitis is the most common ophthalmic association of HL. In the presence of prior known diagnosis of HL, restaging should be considered to exclude recurrence. Toxicity or adverse reaction to drugs used to treat HL may also contribute to ophthalmic involvement.

Photopigment Bleaching Phenomenon With Scanning Laser Ophthalmoscopy and Fluorescein Angiography.

Photopigment bleaching occurs with saturation of photoreceptor pigment by short-wavelength fundus autofluorescence imaging. This phenomenon is seen as characteristic hyperautofluorescence with subsequent imaging acquisition. Herein, a patient with multiple sclerosis was found to exhibit increased choroidal hyperfluorescence during fluorescein angiography (FA) that corresponded with a circumscribed area of intense blue light exposure during initial scanning laser ophthalmoscopy. To the authors' knowledge, this case is the first description of photobleaching phenomenon during FA and should be recognized as nonpathologic by the clinician. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:590-592.].

Biomechanical assessment of radial optic neurotomy.

PURPOSE: A biomechanical model was constructed to simulate the potential therapeutic effect that the surgical procedure radial optic neurotomy (RON) would have on an eye with a central retinal vein occlusion. DESIGN: Experimental study. CONTROLS: Model eyes undergoing RON were compared to control eyes under the same baseline conditions. INTERVENTION: Radial optic neurotomy. We modeled the optic nerve, lamina cribrosa, and the sclera separately and then reassembled the components. Material properties of the sclera and lamina cribrosa were extracted from the literature and both stiff and more elastic values were used for the optic nerve. Intraocular and arterial pressures were varied across a wide range in the analysis. MAIN OUTCOME MEASURE: Change in central retinal vein lumen size. RESULTS: Over a clinically relevant range of boundary conditions, the increase in the lumen area of the central retinal vein lumen after RON remained trivial, ranging from 1% to a maximum of 5%. CONCLUSIONS: The biomechanical effect of RON is negligible, and is unlikely to be a procedure that could mechanically ameliorate the clinical sequelae of a central vein occlusion.

Behçet's disease: comparing 3 decades of treatment response at the National Eye Institute.

BACKGROUND: The goal of the present study was to analyze differences in response to the treatment of ocular Behçet's disease (BD) in the 1960s, 1980s, and 1990s. METHODS: Medical records of 120 patients with uveitis due to BD followed at the National Eye Institute, National Institutes of Health, from 1962 to 2004, were reviewed. RESULTS: The patients were categorized into 3 groups according to the time of follow-up: the first group was followed from 1962 until 1972, the second group from 1983 until 1992, and the third group from 1992 through 2004. Snellen visual acuity was converted to logMAR values. The range of values for inflammation was 0.5 (trace), 1 (mild), 2 (moderate), and 3 (severe). There were 45 patients (89 affected eyes) in the 1960s group, 26 patients (52 eyes) in the 1980s group, and 49 patients (94 eyes) in the most recent group. Statistical analysis showed that the mean logMAR score decreased with each decade. Mean visual acuity in the 1990s group was significantly better than in the previous decades (p < 0.001 for the 1960s group and p = 0.019 for the 1980s). The mean inflammation score was significantly higher in the 1960s than in the subsequent decades (p < 0.001 both for the 1980s and for the 1990s). INTERPRETATION: BD is a severe, blinding disorder. There was a definitive trend toward improvement in clinical outcome from the 1960s to 1990s. We attribute this trend to the introduction of newer, more potent corticosteroid-sparing agents and targeted therapy.