Central serous chorioretinopathy: An evidence-based treatment guideline.

Central serous chorioretinopathy (CSC) is a relatively common disease that causes vision loss due to macular subretinal fluid leakage and it is often associated with reduced vision-related quality of life. In CSC, the leakage of subretinal fluid through defects in the retinal pigment epithelial layer's outer blood-retina barrier appears to occur secondary to choroidal abnormalities and dysfunction. The treatment of CSC is currently the subject of controversy, although recent data obtained from several large randomized controlled trials provide a wealth of new information that can be used to establish a treatment algorithm. Here, we provide a comprehensive overview of our current understanding regarding the pathogenesis of CSC, current therapeutic strategies, and an evidence-based treatment guideline for CSC. In acute CSC, treatment can often be deferred for up to 3-4 months after diagnosis; however, early treatment with either half-dose or half-fluence photodynamic therapy (PDT) with the photosensitive dye verteporfin may be beneficial in selected cases. In chronic CSC, half-dose or half-fluence PDT, which targets the abnormal choroid, should be considered the preferred treatment. If PDT is unavailable, chronic CSC with focal, non-central leakage on angiography may be treated using conventional laser photocoagulation. CSC with concurrent macular neovascularization should be treated with half-dose/half-fluence PDT and/or intravitreal injections of an anti-vascular endothelial growth factor compound. Given the current shortage of verteporfin and the paucity of evidence supporting the efficacy of other treatment options, future studies-ideally, well-designed randomized controlled trials-are needed in order to evaluate new treatment options for CSC.

Outcomes and Clinical Features Predictive of Fungal Endophthalmitis.

PURPOSE: To analyze intravitreal antifungal injections performed at a tertiary center to determine (1) risk factors increasing fungal endophthalmitis likelihood at the time of patient presentation, (2) prognostic factors at presentation, and (3) validity of American Academy of Ophthalmology (Academy) ophthalmologic Candida septicemia (candidemia) screening guidelines. DESIGN: Single-center, retrospective clinical case-control study. METHODS: Clinical course, visual outcome, and final diagnosis were analyzed for 75 patients (81 eyes) receiving intravitreal antifungal injections between 2014 and 2021. Features were compared between fungal endophthalmitis and clinically similar diseases (masquerades). RESULTS: Fungal endophthalmitis was more likely than masquerade based on injection in emergency department or inpatient setting (P = .0002) vs outpatient, greater visual acuity (P = .049), artificial indwelling line present (P = .0004), sepsis within past 6 months (P = .0002), prior/current hepatitis C diagnosis (P = .044), total parenteral nutrition (P = .0028), complicated diabetes mellitus (P = .035), actively treated cancer (P = .021), immunosuppressive medication within past year (P = .035), immunocompromising condition number (P = .031), and delayed pain (P = .0094) and vision loss (P = .020) onset. Visual acuity at presentation correlated with visual outcome (R2 = 0.3524, P = 8.5 × 10-7). No patients with fungal endophthalmitis were asymptomatic or identified by screening. CONCLUSIONS: Many conditions can mimic fungal endophthalmitis, but certain risk factors should raise its suspicion. Regardless of diagnosis, presenting vision correlates with final vision. Lastly, no patients with fungal endophthalmitis were asymptomatic or identified by screening, further supporting current Academy candidemia screening guidelines.

RETINAL RACEMOSE HEMANGIOMA (RETINAL ARTERIOVENOUS COMMUNICATION) DIAGNOSED AND MANAGED WITH MULTIMODAL IMAGING.

BACKGROUND/PURPOSE: Retinal racemose hemangioma is a rare congenital abnormality of the retinal vasculature with a variety of secondary manifestations that can cause vision loss, including macular edema. This report aims to demonstrate the use of swept-source optical coherence tomography angiography in further characterizing this abnormality. METHODS: Case report with multimodal imaging including swept-source optical coherence tomography angiography. RESULTS: A 56-year-old woman with blurred vision was diagnosed macular edema secondary to retinal racemose hemangioma. Localization of the arterial-venous connection was identified with swept-source optical coherence tomography angiography at the deep capillary plexus. Conservative management of the associated foveal exudation ultimately led to a favorable outcome. CONCLUSION: Observation or topical therapy may be useful and warranted in select cases of retinal racemose hemangioma. The anomalous vascular connection in retinal racemose hemangioma seems to originate at the level of the deep capillary plexus in this case; however, larger studies are necessary for corroboration. Evolving angiographic modalities such as swept-source optical coherence tomography angiography may continue to provide insights for this rare disease.

Vitamin A deficiency and the retinal "double carrot" sign with optical coherence tomography.

BACKGROUND: Spectral-domain optical coherence tomography (SD-OCT) and full-field electroretinography (ERG) allow retinal assessment with vitamin A deficiency (VAD). Using SD-OCT, this study aimed to characterize and follow a novel retinal abnormality in patients with VAD and intramuscular supplementation. METHODS: Patients with VAD were retrospectively reviewed, including SD-OCT and electroretinography. RESULTS: Three patients had VAD following bariatric or colon surgery and varying supplementation. All had nyctalopia, extinguished scotopic rod-specific function with ERG, and decreased serum vitamin A. None demonstrated surface abnormalities. All received intramuscular vitamin A with subjective resolution of symptoms. On SD-OCT, four of six eyes exhibited homogenous foveal hyperreflectivity anterior to retinal pigment epithelium-Bruch complex, reminiscent of a "double carrot", which improved following supplementation. ERG findings demonstrated improved scotopic rod-specific function in all cases; however, photopic function remained diminished in two cases. CONCLUSIONS: Structural improvement of the proposed "double carrot" sign occurs soon after vitamin A supplementation. While scotopic function improves rapidly following supplementation, cone function recovers more slowly. Therefore, foveal changes such as the "double carrot" sign suggest that structural recovery of cones precedes functional recovery.

Risk factors for enucleation or evisceration in endophthalmitis.

PURPOSE: To identify clinical risk factors for enucleation or evisceration in patients with endophthalmitis at an academic institution. METHODS: A retrospective review of patients diagnosed with endophthalmitis at Wilmer Eye Institute from 2010 to 2019 was conducted. Clinical characteristics, including demographics, cause for endophthalmitis, microbial culture results, salvaging procedures and surgical intervention were recorded. In patients who underwent enucleation or evisceration, type of surgery and placement of a primary implant were recorded. Chi-squared, Student's t-tests and multivariate analysis were used to identify clinical factors that predicted enucleation or evisceration. RESULTS: Two hundred and fifty three patients treated for endophthalmitis over the study period were identified, of which 25 (9.88%) underwent enucleation or evisceration. Risk factors for enucleation or evisceration included poor presenting visual acuity (OR 7.86, CI: 2.26, 27.3), high presenting intraocular pressure (OR 1.07, CI: 1.03, 1.12), presence of relative afferent pupillary defect (OR 3.69, CI: 1.20, 11.37) and positive vitreous culture for methicillin-resistant staphylococcus aureus (MRSA) (OR 18.3, CI: 1.54, 219.2) on multivariate analysis. Patients undergoing enucleation or evisceration were also more likely to have trauma, corneal ulcer or combined causes for endophthalmitis and underwent fewer salvaging surgical and procedural interventions. There were no significant differences in characteristics of those receiving enucleation versus evisceration in our cohort. CONCLUSION: Patients with endophthalmitis who underwent enucleation or evisceration had more severe disease on presentation compared to those treated with eye sparing therapy. Presenting clinical characteristics may have a role in triage and management decisions for patients presenting with severe endophthalmitis.

Intraocular Metastasis of Large T-cell Lymphoma Transformed from Mycosis Fungoides.

PURPOSE: To describe a rare case of intraocular lymphoma that metastasized from cutaneous mycosis fungoides and transformed to large cell T cell lymphoma resulting in vitreoretinal pathology. METHODS: Retrospective case report. RESULTS: A 57-year-old male presented with 3 months of blurred vision in the right eye. He reported only a medical history of psoriasis. Examination revealed keratic precipitates and dense vitritis in the right eye. He was taken for a diagnostic vitrectomy. Histopathology showed that atypical lymphoid cells and flow cytometry were consistent with transformed large cell T-cell lymphoma. During follow-up, pre- and inner retinal lesions were noted throughout the posterior pole. Histopathology of the psoriatic lesions was consistent with mycosis fungoides. He was initiated on systemic and intravitreal methotrexate with improvement in vision. CONCLUSIONS: Ocular involvement in metastatic transformed T-cell lymphoma is extremely rare but can be present with vitritis and retinal deposits. Our patient responded well to intravitreal methotrexate therapy.

Culture of Human Retinal Explants for Ex Vivo Assessment of AAV Gene Delivery.

Due to the clinically established safety and efficacy profile of recombinant adeno-associated viral (rAAV) vectors, they are considered the "go to" vector for retinal gene therapy. Design of a rAAV-mediated gene therapy focuses on cell tropism, high transduction efficiency, and high transgene expression levels to achieve the lowest therapeutic treatment dosage and avoid toxicity. Human retinal explants are a clinically relevant model system for exploring these aspects of rAAV-mediated gene delivery. In this chapter, we describe an ex vivo human retinal explant culture protocol to evaluate transgene expression in order to determine the selectivity and efficacy of rAAV vectors for human retinal gene therapy.

Surgical Approach with Pars Plana Vitrectomy for Subretinal Gene Therapy.

Gene therapy is emerging as a treatment for inherited diseases including retinitis pigmentosa. Through surgery, specifically with pars plana vitrectomy, the subretinal space can be accessed to directly administer this treatment. The goal herein is to provide an overview of this approach.

Characterizing the microbiota of instrumentation in ophthalmology clinics during and beyond the COVID-19 pandemic.

PURPOSE: Increased ophthalmology-specific risk of novel coronavirus 2019 (SARS-CoV-2) transmission is well-established, increasing the fear of infection and causing associated decreased rates of procedures known to save vision. However, the potential transmission from exposure to clinic instrumentation is unknown, including which additional pathogens may be spreading in this context. This study seeks to fill this gap by characterizing the microbiota of instrumentation in ophthalmology clinics during the COVID-19 pandemic and identifying potential sources of pathogenic spread encountered by patients and healthcare workers. METHODS: Thirty-three samples were captured using standard cultures and media. Ten positive and negative controls were used to confirm proper technique. Descriptive statistics were calculated for all samples. Samples were collected from the retina (N = 17), glaucoma (N = 6), cornea (N = 6), and resident (N = 4) clinics with rigorous disinfection standards at a tertiary academic medical center. Standard media cultures and/or polymerase chain reaction (PCR) was performed for each sample. RESULTS: From 33 samples, more than half (17/33, 51.5%) yielded bacterial growth. Using two different molecular methods, three samples (3/33, 9%) tested positive for SARS-CoV-2 (cycle thresholds 36.48, 37.14, and 37.83). There was no significant difference in bacterial growth (95% confidence interval [95% CI]: - 0.644-0.358, p = 0.076) among different clinics (retina, glaucoma, cornea, resident). Staphylococcus (S.) epidermidis grew most frequently (12/35, 34%), followed by S. capitis (7/35, 20%), Micrococcus luteus (2/35, 5.7%), Corynebacterium tuberculostearicum (2/35, 5.7%), and Cutibacterium ([C.], Propionibacterium) acnes (2/35, 5.7%). C. acnes growth was more frequent with imaging device forehead rests (2/7, 28.6%) than other surfaces (0/26, 0%, 95% CI: 0.019-0.619, p = 0.040). No samples isolated fungus or adenovirus. CONCLUSIONS: Most samples across subspecialty clinic instrumentation grew bacteria, and several tested positive for SARS-CoV-2. Many isolated pathogens have been implicated in causing infections such as endophthalmitis, conjunctivitis, uveitis, and keratitis. The clinical implications of the ophthalmology microbiome for transmitting nosocomial infections warrant optimization of disinfection practices, strategies for mitigating spread, and additional study beyond the pandemic.

TRIPLE THERAPY WITH RITUXIMAB, INTRAVENOUS IMMUNOGLOBULIN, AND INTRAVITREAL CORTICOSTEROIDS FOR MELANOMA-ASSOCIATED RETINOPATHY: TTRIIC DOES THE TRICK.

PURPOSE: Melanoma-associated retinopathy responds poorly to currently-available therapies, with continued chronic decline in visual function being the norm, despite treatment. The purpose of this report is to describe the excellent response of a patient with melanoma-associated retinopathy to a triple therapy regimen of rituximab, intravenous immunoglobulin, and intravitreal corticosteroids. METHODS: Single interventional case report describing management of melanoma-associated retinopathy and the patient's response to this treatment. Retinal function was monitored by serial visual acuity, fundus exams, Goldmann visual fields, and electroretinography. RESULTS: A 65-year old man presented with new onset photopsia, decrease visual acuity and nyctalopia in both eyes in the setting of recently-diagnosed Stage IIIB melanoma, initially treated with wide local excision and adjuvant interferon. He was diagnosed with melanoma-associated retinopathy that initially worsened during his course of interferon for treatment of the melanoma. We initiated triple therapy with rituximab, intravenous immunoglobulin, and intravitreal corticosteroids, and this resulted in full return of electroretinography function and resumption of 20/20 visual acuity in both eyes. CONCLUSION: This is the first reported case of the utility of triple therapy with rituximab, intravenous immunoglobulin, and intravitreal steroids for successful management of melanoma-associated retinopathy as demonstrated by improvement in acuity, symptoms, visual fields, and electroretinography.

American Academy of Ophthalmology Recommendations on Screening for Endogenous Candida Endophthalmitis.

The American Academy of Ophthalmology evaluated the practice of routine screening for intraocular infection from Candida septicemia. In the United States, ophthalmologists are consulted in the hospital to screen for intraocular infection routinely for patients with Candida bloodstream infections. This practice was established in the era before the use of systemic antifungal medication and the establishment of definitions of ocular disease with candidemia. A recent systematic review found a rate of less than 1% of routinely screened patients with endophthalmitis from Candida septicemia. Other studies found higher rates of endophthalmitis but had limitations in terms of inaccuracies in ocular disease classification, lack of vitreous biopsies, selection biases, and lack of longer-term visual outcomes. Some studies attributed ocular findings to Candida infections, rather than other comorbidities. Studies also have not demonstrated differences in medical management that are modified for eye disease treatment; therefore, therapy should be dictated by the underlying Candida infection, rather than be tailored on the basis of ocular findings. In summary, the Academy does not recommend a routine ophthalmologic consultation after laboratory findings of systemic Candida septicemia, which appears to be a low-value practice. An ophthalmologic consultation is a reasonable practice for a patient with signs or symptoms suggestive of ocular infection regardless of Candida septicemia.

Frequency of Urgent or Emergent Vitreoretinal Surgical Procedures in the United States During the COVID-19 Pandemic.

Importance: The American Academy of Ophthalmology (AAO) indicated that urgent or emergent vitreoretinal surgical procedures should continue during the coronavirus disease 2019 (COVID-19) pandemic. Although decreases in the frequency of critical procedures have been reported outside the field of ophthalmology, analyses are limited by volume, geography, and time. Objective: To evaluate whether the frequency of ophthalmic surgical procedures deemed urgent or emergent by the AAO changed across the United States during the COVID-19 pandemic. Design, Setting, and Participants: Vitreoretinal practices from 17 institutions throughout the US participated in this multicenter cross-sectional study. The frequency of 11 billed vitreoretinal Current Procedural Terminology (CPT) codes across respective weeks was obtained from each practice between January 1, 2019, and May 31, 2020. Data were clustered into intravitreal injections (code 67028), lasers and cryotherapy (codes 67141, 67145, and 67228), retinal detachment (RD) repairs (codes 67107, 67108, 67110, and 67113), and other vitrectomies (codes 67036, 67039, and 67040). Institutions were categorized by region (Northeast, Midwest, South, and West Coast), practice setting (academic [tax-exempt] or private [non-tax-exempt]), and date of respective statewide stay-at-home orders. Main Outcomes and Measures: Nationwide changes in the frequency of billing for urgent or emergent vitreoretinal surgical procedures during the COVID-19 pandemic. Results: A total of 526 536 CPT codes were ascertained: 483 313 injections, 19 257 lasers or cryotherapy, 14 949 RD repairs, and 9017 other vitrectomies. Relative to 2019, a weekly institutional decrease in injections was observed from March 30 to May 2, 2020, with a maximal 38.6% decrease (from a mean [SD] of 437.8 [436.3] to 273.8 [269.0] injections) from April 6 to 12, 2020 (95% CI, -259 to -69 injections; P = .002). A weekly decrease was also identified that spanned a longer interval, at least until study conclusion (March 16 to May 31, 2020), for lasers and cryotherapy, with a maximal 79.6% decrease (from a mean [SD] of 6.6 [7.7] to 1.5 [2.0] procedures) from April 6 to 12, 2020 (95% CI, -6.8 to -3.3 procedures; P < .001), for RD repairs, with a maximal 59.4% decrease (from a mean [SD] of 3.5 [4.0] to 1.6 [2.2] repairs) from April 13 to 19, 2020 (95% CI, -2.7 to -1.4 repairs; P < .001), and for other vitrectomies, with a maximal 84.3% decrease (from a mean [SD] of 3.0 [3.1] to 0.4 [0.8] other vitrectomies) from April 6 to 12, 2020 (95% CI, -3.3 to -1.8 other vitrectomies; P < .001). No differences were identified by region, setting, or state-level stay-at-home order adjustment. Conclusions and Relevance: Although the AAO endorsed the continued performance of urgent or emergent vitreoretinal surgical procedures, the frequency of such procedures throughout the country experienced a substantial decrease that may persist after the COVID-19 pandemic's initial exponential growth phase. This decrease appears independent of region, setting, and state-level stay-at-home orders. It is unknown to what extent vitreoretinal intervention would have decreased without AAO recommendations, and how the decrease is associated with outcomes. Although safety is paramount during the COVID-19 pandemic, practices should consider prioritizing availability for managing high-acuity conditions until underlying reasons for the reduction are fully appreciated.

Blunderbuss: Ocular and Orbital Injuries Due to Muzzle-Loading Firearms.

PURPOSE: Injury to the eye and/or orbital and adnexal structures associated with antiquated muzzle-loading firearms has not, to our knowledge, been characterized with the exception of a single case report. METHODS: A retrospective chart review of 7 patients treated at Vanderbilt University Medical Center from 2003 to 2017 who sustained traumatic injuries to the ocular and/or orbital structures secondary to the discharge of muzzle-loading firearms. The study was approved by the Vanderbilt Institutional Review Board. RESULTS: In 6/7 cases, injuries occurred secondary to the muzzle-loading firearm exploding due to dysfunction or misuse. Foreign material deriving from the firearm was retained in 3/7 patients. Initial examination of the orbit and adnexa revealed 5/7 individuals sustaining orbital fractures and 6/7 with facial lacerations (including 2 with eyelid lacerations); none had evidence of a lacrimal duct injury. Three patients suffered globe injuries (1 closed-globe and 2 open-globe). Visual acuity at last follow-up was ≥20/20 in 12/14 eyes examined. Surgical intervention was required in the treatment of 4/7 individuals (including 3/7 requiring intervention for sustained orbital fractures). No individuals were wearing eye protection at the time of injury. All individuals survived their injuries. CONCLUSIONS: The operation of muzzle-loading firearms poses a unique risk of injury to the operator. The resultant injuries in this case series were primarily due to the explosion of the firearm, which subsequently appear similar to orbital and ocular blast injuries caused by explosive weapons. Orbital injuries and more potentially more devastating ocular injuries may have been prevented by protective eyewear.

Bacillary Layer Detachment in Bilateral Diffuse Uveal Melanocytic Proliferation Masquerading as Neovascular AMD.

Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare and unusual paraneoplastic ocular syndrome with generally poor prognosis. The authors present a case of BDUMP in a patient with bladder cancer, examined with current multimodal imaging. In the clinical setting with drusen and exudative macular detachments, the fundus simulated neovascular age-related macular degeneration, warranting standard-of-care therapy. The imaging actually showed the typical manifestations of BDUMP, but also newly recognized, associated manifestations, including the bacillary layer detachment, a gravitating retinal detachment, and multifocal choroidal hyperpermeability, but no evidence of neovascularization. Recognition of these associated manifestations is of value in appreciating the pathophysiology of this paraneoplastic disorder. Based on the imaging, the correct diagnosis was possible along with a better understanding of the nature of the clinical features in the posterior fundus. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:413-417.].

Novel REEP6 gene mutation associated with autosomal recessive retinitis pigmentosa.

PURPOSE: This study reports the ophthalmic and genetic findings of a Cameroonian patient with autosomal recessive retinitis pigmentosa (arRP) caused by a novel Receptor Expression Enhancing Protein 6 (REEP6) homozygous mutation. PATIENT AND METHODS: A 33-year-old man underwent comprehensive ophthalmic examinations, including visual acuity measurements, dilated fundus imaging, electroretinography (ERG), and spectral-domain optical coherence tomography (SD-OCT). Short-wavelength fundus autofluorescence (SW-AF) and near-infrared fundus autofluorescence (NIR-AF) were also evaluated. Whole exome sequencing (WES) was used to identify potential pathogenic variants. RESULTS: Fundus examination revealed typical RP findings with additional temporal ten micron yellow dots. SD-OCT imaging revealed cystoid macular edema and perifoveal outer retinal atrophy with centrally preserved inner segment ellipsoid zone (EZ) bands. Hyperreflective spots were seen in the inner retinal layers. On SW-AF images, a hypoautofluorescent area in the perifoveal area was observed. NIR-AF imaging revealed an irregularly shaped hyperautofluorescent ring. His visual acuity was mildly affected. ERG showed undetectable rod responses and intact cone responses. Genetic testing via WES revealed a novel homozygous mutation (c.295G>A, p.Glu99Lys) in the gene encoding REEP6, which is predicted to alter the charge in the transmembrane helix. CONCLUSIONS: This report is not only the first description of a Cameroonian patient with arRP associated with a REEP6 mutation, but also this particular genetic alteration. Substitution of p.Glu99Lys in REEP6 likely disrupts the interactions between REEP6 and the ER membrane. NIR-AF imaging may be particularly useful for assessing functional photoreceptor cells and show an "avocado" pattern of hyperautofluorescence in patients with the REEP6 mutation.

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.].

Novel FOXC2 Mutation and Distichiasis in a Patient With Lymphedema-Distichiasis Syndrome.

A 4 year-old-boy was referred for distichiasis of the upper and lower lids of both eyes that had been present since at least 1 year of age. The patient's family history was notable for distichiasis and lymphedema affecting numerous family members. The patient was found to have a novel heterozygous variant (c.741_742insGG) in the FOXC2 gene. Mutations in the FOXC2 gene are associated with lymphedema-distichiasis syndrome. An important feature of lymphedema-distichiasis syndrome is that distichiasis is typically present prior to the onset of lymphedema.