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 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) combined 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.

Multimodal Imaging of a novel MFSD8/CLN7 mutation associated with non-syndromic symmetric adult-onset macular dystrophy.

PURPOSE: To report multimodal imaging features of a novel MFSD8/CLN7 pathogenic variant associated with bilateral and symmetric non-syndromic macular dystrophy. METHODS: A 63-year-old female patient presented complaining of a gradual subjective decline in visual acuity in both eyes over the previous months. This patient underwent a comprehensive ophthalmological assessment, including multimodal retinal imaging and electrophysiological testing. Given suspicion for a hereditary retinal disorder, genetic testing was pursued. RESULTS: The eye examination revealed blunted foveal reflexes and no lesions or abnormalities in the equatorial or anterior retinal periphery. Multimodal imaging showed a bilateral and almost symmetrical subfoveal interruption of the outer retinal layers including an optical gap. Genetic testing revealed that the MFSD8/CLN7 gene exhibited a homozygous variant, specifically p.Ala484Val (c.1451C>T). This variant was identified as the likely causative factor for the condition. CONCLUSION: We herein describe the clinical findings of a previously unreported homozygous variant in the MFSD8/CLN7 gene, resulting in a non-syndromic form of bilateral central macular dystrophy.

Use of a subpalpebral lavage system as salvage therapy for Pseudomonas aeruginosa panophthalmitis due to an infected scleral buckle.

PURPOSE: To present a case and surgical technique for management of Pseudomonas aeruginosa panophthalmitis secondary to an infected scleral buckle. METHODS: Surgical technique video for management of an infected scleral buckle resulting in panophthalmitis with scleral buckle and suture explant and insertion of a subpalpebral lavage system. RESULTS: After two months, the visual acuity was restored to hand motion, likely secondary to a fibrotic secondary membrane, and the retina remain attached. This reports the first description of globe salvage for panophthalmitis from a P. aeruginosa-infected scleral buckle. CONCLUSION: This case encourages surgeons to remove all aspects of an exposed scleral buckle, including sutures, and emphasizes the importance of routine culture of all explanted material, even in the absence of clinical infection. In addition, this case encourages the use of a subpalpebral lavage in cases of severe P. aeruginosa ocular infections.

Characterization of Ocular Injuries Caused by Orbeez Hydrated Gel Pellet Projectiles: Clinical Insights and Implications.

PURPOSE: To examine the clinical characteristics of patients who have experienced blunt ocular injuries from "Orbeez" hydrated gel pellets (Spin Master Corp.), and to describe ocular morbidity, visual acuity (VA), and intraocular pressure (IOP) after Orbeez-related ocular trauma. DESIGN: Retrospective, institutional, observational case series. METHODS: Patients sustaining Orbeez-related ocular trauma at a single institution over a 13-month period were identified. Clinical parameters including VA, IOP, and anterior and fundus examination findings were assessed upon initial and final presentation. Basic statistical testing was performed to compare differences within this cohort. RESULTS: A total of 17 eyes from 17 patients with Orbeez-related trauma were identified. Orbeez-related blunt ocular injuries included corneal abrasion (n = 7), hyphema (n = 9), commotio retinae (n = 5), intraretinal hemorrhage (n = 3), preretinal hemorrhage (n = 1), vitreous hemorrhage (n = 2), and retinal tear (n = 1). Adolescents (14-18 years of age) showed higher rates of posterior segment complications compared to other ages (P = .0152). The presence of elevated IOP and hyphema upon initial examination correlated with increased likelihood of requiring invasive treatment following Orbeez impact (P = .0275). CONCLUSION: Orbeez-related ocular trauma may be associated with severe visual morbidity and varied anterior and posterior segment intraocular sequelae. Adolescents could be at increased risk for posterior segment complications following these injuries. Initial findings of elevated IOP and hyphema may indicate a need for more aggressive interventions. Prevention remains paramount in managing Orbeez-related ocular trauma; it is critical to raise awareness regarding the importance of wearing eye protection meeting high-impact standards and minimizing exposure to such projectiles.

The Sensitivity of Ultra-Widefield Fundus Photography Versus Scleral Depressed Examination for Detection of Retinal Horseshoe Tears.

PURPOSE: Ultra-widefield (UWF) imaging is commonly used in ophthalmology in tandem with scleral depressed examinations (SDE) to evaluate peripheral retinal disease. Because of the increased reliance on this technology in tele-ophthalmology, it is critical to evaluate its efficacy for detecting the peripheral retina when performed in isolation. Therefore, we sought to evaluate UWF imaging sensitivity in detecting retinal horseshoe tears (HSTs). STUDY DESIGN: Retrospective clinical validity and reliability study. METHODS: A single-institutional retrospective analysis was performed on patients at the Shiley Eye Institute, University of California, San Diego. Patients with HSTs seen on SDE who underwent treatment with laser were included in the study. A total of 140 patients with HSTs in the right and/or left eyes met the inclusion criteria. Those with concomitant ruptured globes, retinal detachments, and vitreous hemorrhages were excluded. A total of 123 patients with 135 HSTs were included in the final analysis. The primary outcome was the number of HSTs detected by UWF imaging. A secondary outcome was HST location. Sensitivity was measured with respect to HST location, and statistical significance was calculated by Fisher exact testing. RESULTS: A total of 69 (51.1%) HSTs were visualized on UWF images and 66 (48.9%) were not visualized. The sensitivity of UWF imaging in capturing HSTs was 7 of 41 (17.1%), 8 of 25 (32.0%), 7 of 14 (50.0%), and 47 of 55 (85.5%) for the superior, inferior, nasal, and temporal quadrants, respectively. Sensitivities between HST visibility and location were statistically significant (P < .001). CONCLUSIONS: Nearly half of HSTs were missed by UWF imaging. This study demonstrates that UWF imaging alone is not sufficiently sensitive to exclude the presence of HSTs.

Expanded Spectrum Torpedo Retinopathy: A Case Series.

Torpedo lesions in the retina are rare, and their clinical significance has not been well established. This case series highlights patients with atypical torpedo lesions with varying orientations and pigmentation patterns. We describe the first documented case of an inferiorly oriented lesion, to our knowledge, and add to the few previous descriptions of double-torpedo lesions.

Phenotypic Variability of Retinal Disease Among a Cohort of Patients With Variants in the CLN Genes.

Purpose: To describe the phenotype of CLN-associated retinal dystrophy in a subset of patients at the Columbia University Medical Center, United States, and the Hospital das Clínicas de Pernambuco, Brazil, in comparison to the published literature. Methods: Eleven patients with confirmed biallelic variants in the CLN genes were evaluated via dilated fundus examination, clinical imaging, and full-field electroretinogram. A thorough literature search was conducted to determine previously published variants and associated phenotypes. Results: Genetic testing confirmed the presence of variants in CLN3, CLN7/MFSD8, CLN8, and GRN/CLN11. Five novel variants were identified, and four novel phenotypes of previously published alleles were described. The phenotype differed among patients with variants in the same gene and sometimes among patients with the same allele. Conclusions: Substantial phenotypic variability among variants in the CLN genes makes identification of genotype-phenotype or allele-phenotype correlations challenging. Further study is required to establish an extensive database for adequate patient counseling.

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.

OCT and OCT Angiography Update: Clinical Application to Age-Related Macular Degeneration, Central Serous Chorioretinopathy, Macular Telangiectasia, and Diabetic Retinopathy.

Similar to ultrasound adapting soundwaves to depict the inner structures and tissues, optical coherence tomography (OCT) utilizes low coherence light waves to assess characteristics in the eye. Compared to the previous gold standard diagnostic imaging fluorescein angiography, OCT is a noninvasive imaging modality that generates images of ocular tissues at a rapid speed. Two commonly used iterations of OCT include spectral-domain (SD) and swept-source (SS). Each comes with different wavelengths and tissue penetration capacities. OCT angiography (OCTA) is a functional extension of the OCT. It generates a large number of pixels to capture the tissue and underlying blood flow. This allows OCTA to measure ischemia and demarcation of the vasculature in a wide range of conditions. This review focused on the study of four commonly encountered diseases involving the retina including age-related macular degeneration (AMD), diabetic retinopathy (DR), central serous chorioretinopathy (CSC), and macular telangiectasia (MacTel). Modern imaging techniques including SD-OCT, TD-OCT, SS-OCT, and OCTA assist with understanding the disease pathogenesis and natural history of disease progression, in addition to routine diagnosis and management in the clinical setting. Finally, this review compares each imaging technique's limitations and potential refinements.

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.

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.

Novel MFSD8 mutation causing non-syndromic asymmetric adult-onset macular dystrophy.

BACKGROUND: MFSD8 mutations can cause type 7 neuronal ceroid lipofuscinosis, a systemic disorder that includes vision loss; however, such mutations can also cause isolated retinal dystrophy with vision loss without systemic signs or symptoms as first identified in 2015. This report details a previously unreported combination of compound heterozygous variants in the MFSD8 gene causing a non-syndromic, bilateral central macular dystrophy presenting in adulthood. MATERIALS AND METHODS: We present a case of MFSD8-associated retinal dystrophy with multimodal imaging and a review of relevant literature. RESULTS: A 57-year-old female presented for subacute, unilateral blurriness in her right eye. Best corrected visual acuity was 20/250 and 20/50 in the right and left eyes, respectively. Fundus examination and multimodal imaging revealed blunted foveal reflexes and optical gap with subfoveal ellipsoid zone loss in both eyes, right greater than left. Full field electroretinography results were within normal limits while the Arden ratio on electro-oculography was abnormal in both eyes, right more so than left. Genetic testing revealed apparently causative compound heterozygous mutations in the MFSD8 gene: c.154G>A, p.(Gly52Arg) and c.1006G>C, p.(Gluc336Gln). Visual acuity over one year of follow-up has remained stable. CONCLUSIONS: To authors' knowledge, this report is first description of this combination of mutations in the MFSD8 gene leading to non-syndromic adult-onset macular dystrophy.

Etiology of Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is a set of symptoms including tunnel vision, night blindness, and progressive vision loss, stemming from a very heterogeneous set of causes-it can result from a several different kinds of mutations (non-syndromic) in conjunction with other symptoms, as part of a larger syndrome (syndromic), or secondary to an organ system disease state (secondary RP). This chapter explores and elucidates these various causes of RP.

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.

National emergency department trends for endogenous endophthalmitis: an increasing public health challenge.

BACKGROUND/OBJECTIVE: To characterize incidence rates and identify risk factors for admission and mortality in patients with endogenous endophthalmitis (EE) in the United States (US). SUBJECTS/METHODS: Patients with EE were identified using the Nationwide Emergency Department (NEDS) Database from 2006 to 2017 in this cross-sectional study. Subjects were required to have diagnoses of both endophthalmitis and septicaemia using contemporary International Classification of Diseases diagnosis codes. Incidence rates, mortality rates and demographics were evaluated. Risk factors for admission and mortality were identified using weighted logistic regression analysis. RESULTS: A total of 6400 patients with EE were identified. Incidence increased from 0.10 (95% confidence interval [CI]: 0.07-0.12) per 100,000 in the US population in 2006 to 0.25 (95% CI: 0.21-0.30) in 2017 (p < 0.05). Most were female (55.4%), insured with Medicare (53.5%), were in the first income quartile earnings (29.3%) [bottom 25% income bracket], lived in the South (40.5%), and presented to metropolitan teaching hospitals (66.6%). Mortality increased from 8.6% (95% CI: 3.8-18.3%) in 2006 to 13.8% (95% CI: 9.7-19.2%) in 2017 (p = 0.94). Factors predicting admission included older age (odds ratio [OR] 32.59; [95% CI 2.95-359.78]) and intravenous drug use (OR 14.90 [95% CI: 1.67-133.16]). Factors associated with increased mortality included: human immunodeficiency virus infection/immune deficiencies (OR 2.58 [95% CI: 1.26-5.28]), heart failure (OR 2.12 [95% CI: 1.47-3.05]), and hepatic infections/cirrhosis (OR 1.89 [95% CI: 1.28-2.79]). Pneumonia and renal/urinary tract infections (UTI) were associated with both increased hospital admission [(pneumonia OR 9.64 (95% CI: 1.25-74.35, p = 0.030), renal/UTI OR 4.09 (95% CI: 1.77-9.48)] and mortality [(pneumonia OR 1.64 (95% CI: 1.17-2.29, p = 0.030), renal/UTI OR 1.87 (95% CI: 1.18-2.97)]. Patients with diabetes mellitus (DM) had decreased odds ratio for mortality (OR 0.49 [95% CI: 0.33-0.73]). CONCLUSION: EE has increased in incidence throughout US. The two systemic factors that conferred both an increase in mortality and admission were pneumonia, and renal/UTI. Additional exploration of the potential protective association of DM with decreased mortality in this context is needed.

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.

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.