Faculty Bibliography

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.

PURPOSE/OBJECTIVE:Retinal racemose hemangioma (RRH) 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 utility of swept-source optical coherence tomography angiography (SS-OCTA) in further characterizing this abnormality. METHODS:Case report with multimodal imaging including SS-OCTA. RESULTS:A 56-year-old woman with blurred vision was diagnosed macular edema secondary to RRH. Localization of the arterial-venous connection was identified with SS-OCTA at the deep capillary plexus (DCP). Conservative management of the associated foveal exudation ultimately led to a favorable outcome. DISCUSSION/CONCLUSIONS:Observation or topical therapy may be useful and warranted in select cases of RRH. The anomalous vascular connection in RRH appears to originate at the level of the DCP in this case, however larger studies are necessary for corroboration. Evolving angiographic modalities like SS-OCTA may continue to provide insights for this rare disease.

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.

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.

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.

PURPOSE/OBJECTIVE:To describe clinical features including multimodal imaging in a rare case of presumed embolic cilioretinal artery occlusion with long-term follow-up examination. METHODS:A 61-year-old man presented after noticing an acute-onset central scotoma in the left eye during coronary arteriography. Fundus color photography, red-free imaging, near-infrared reflectance, spectral domain optical coherence tomography (OCT), fluorescein angiography, and swept-source OCT angiography were performed. RESULTS:Color and red-free fundus imaging both showed retinal whitening in the territory corresponding to a cilioretinal artery in the left eye. Consistent with an ischemic event, the near-infrared reflectance showed a hyporeflective area in the same location. Spectral domain OCT showed hyperreflectivity and generalized thickening of the inner nuclear layer, ganglion cell layer, and retinal nerve fiber layer. Seven years later, color, red-free, and near-infrared reflectance imaging appeared normal, but the spectral domain OCT showed thinning of all retinal layers in the affected area. Furthermore, swept-source OCT angiography demonstrated markedly reduced capillary flow signal in the superficial and deep capillary plexuses, corresponding to a persistent scotoma described by the patient. CONCLUSION/CONCLUSIONS:This case report illustrates hallmark features of a rare presumed embolic cilioretinal artery occlusion and its long-term manifestations with thorough historical and multimodal imaging data. When standard fundus imaging with color, red-free, and near-infrared reflectance appears normal years after a retinal vascular insult, OCT and OCT angiography can corroborate a patient's persistent visual deficit and provide clarity to the diagnosis.

PURPOSE/UNASSIGNED: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/UNASSIGNED:Retrospective case report. RESULTS/UNASSIGNED: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/UNASSIGNED: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.

PURPOSE/OBJECTIVE:To report new multimodal imaging features that enhance our understanding of the inflammatory and ischemic nature of acute idiopathic maculopathy (AIM) and to correlate structural and functional changes due to a reversible initial choroidal ischemia over a clinical course of 3.5 months. METHODS:A 31-year-old man presented with acute central vision loss in his right eye due to coxsackievirus-associated AIM. Serial multimodal retinal imaging including confocal true color fundus photography, blue-light fundus autofluorescence (BAF), near-infrared reflectance (NIR), spectral domain optical coherence tomography and swept-source optical coherence tomography (SD-OCT + SS-OCT), and en face SS-OCT angiography (SS-OCTA) were performed over a 3.5-month follow-up. Eidon true color confocal scanner camera (Centervue, Padova, Italy) was used for color and BAF imaging. Near-infrared reflectance and SD-OCT images were obtained with the Heidelberg Spectralis OCT (HRA2 + OCT; Heidelberg Engineering, Heidelberg, Germany). For SS-OCT and en face SS-OCT and SS-OCTA images, the PLEX Elite 9,000 (Carl Zeiss Meditec, Inc, Dublin, CA) was used. Central alterations in choriocapillaris flow were analyzed with SS-OCTA using the University of Washington choriocapillaris (CC) flow deficit quantification algorithm available through the ARI Network. Flow deficit area and density values were analyzed and compared between the first and last examinations. Corresponding en face OCT imaging was used to distinguish true flow defects from artifacts secondary to shadowing. RESULTS:In the acute stage of AIM, a bacillary layer detachment appearing as a yellow-grayish foveal elevation surrounded by a hypopigmented parafoveal ring was evident in a Bull's eye configuration, corresponding to a hyperreflective ring upon NIR and a hyperautofluorescent ring with BAF. SD + SS-OCT showed mostly intraretinal fluid consistent with a bacillary layer detachment in conjunction with a thickened inner choroid. At presentation, SS-OCTA demonstrated a marked reduction of choriocapillaris flow signal. At 1 week, early resolution of retinal fluid was followed by restoration of the ellipsoid zone at 5 weeks, while restoration of the interdigitation zone and reduction in retinal pigment epithelium/Bruch membrane complex thickening occurred more slowly. Swept-source OCT angiography showed a gradual, but incomplete, recovery of inner choroidal flow signal at 3.5-month follow-up. CONCLUSION/CONCLUSIONS:Acutely, AIM may present with a photoreceptor splitting foveal bacillary layer detachment associated with a marked reduction in inner choroidal flow signal on SS-OCTA. Thereafter, restoration of the outer retinal layers and gradual normalization of choroidal flow signal appear to support the often-benign nature of the disease.