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Hypoxia‐inducible factor (HIF) plays a critical role in the mechanisms that allow cells to adapt to various oxygen levels in the environment. Specifically, HIF‐1⍺ has shown to be widely involved in cellular repair, survival, and energy metabolism. HIF‐1⍺ has also been found in increased levels in cancer cells, highlighting the importance of balance in the hypoxic response. Promoting HIF‐1⍺ activity as a potential therapy for degenerative diseases and inhibiting HIF‐1⍺ as a therapy for pathologies with overactive cell proliferation are actively being explored. Digoxin and metformin, HIF‐1⍺ inhibitors, and deferoxamine and ⍺‐ketoglutarate analogues, HIF‐1⍺ activators, are being studied for application in age‐related macular degeneration, diabetic retinopathy, and retinitis pigmentosa. However, these same medications have retinal toxicities that must be assessed before implementation of therapeutic care. Herein, we highlight the duality of therapeutic and toxic potential of HIF‐1⍺ that must be carefully assessed prior to its clinical application in retinal disorders. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has galvanized the development of new vaccines at an unprecedented pace. Since the widespread implementation of vaccination campaigns, reports of ocular adverse effects after COVID-19 vaccinations have emerged. This review summarizes ocular adverse effects possibly associated with COVID-19 vaccination, and discusses their clinical characteristics and management. Narrative Literature Review. Ocular adverse effects of COVID-19 vaccinations include facial nerve palsy, abducens nerve palsy, acute macular neuroretinopathy, central serous retinopathy, thrombosis, uveitis, multiple evanescent white dot syndrome, Vogt-Koyanagi-Harada disease reactivation, and new-onset Graves' Disease. Studies in current literature are primarily retrospective case series or isolated case reports – these are inherently weak in establishing association or causality. Nevertheless, the described presentations resemble the reported ocular manifestations of the COVID-19 disease itself. Hence, we hypothesize that the human body's immune response to COVID-19 vaccinations may be involved in the pathogenesis of the ocular adverse effects post-COVID-19 vaccination. Ophthalmologists and generalists should be aware of the possible, albeit rare, ocular adverse effects after COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

Purpose: To report a novel case of Paracentral Acute Middle Maculopathy (PAMM) Secondary to Retinal Artery Macroaneurysm. Methods: A case report. Results: A 72‐year‐old lady presented with three‐month history of sudden onset left paracentral scotoma. Her medical history include hypertension and hyperlipidemia. Visual acuity was 6/7.5 and 6/45 in the right and left eye respectively. Anterior segment examination and intraocular pressures were unremarkable. A ruptured retinal arterial macroaneurysm (RAM) was seen along the second‐order artery along the inferotemporal arcade with a small area of deep‐retinal whitening along the distal branches of the artery. Corresponding optical coherence tomography showed a round superficial retinal hyperreflective lesion consistent with RAM and hyperreflective band involving the outer plexiform layer (OPL), inner nuclear layer (INL) and inner plexiform layer (IPL) consistent with PAMM. Confocal scanning laser ophthalmoscopy video fluorescein angiogram (FA) demonstrated a ruptured and hemorrhagic RAM with significantly delayed distal filling of the artery, with resultant PAMM in an area supplied by the tributary arterioles of the affected artery. Conclusions: Oxygen consumption is highest at the metabolically active middle retinal layer. The inner and middle retinal layers are supplied by the superficial capillary plexus in the ganglion cell layer, intermediate capillary plexus (ICP) in the INL‐IPL boundary and deep capillary plexus (DCP) in the INL‐OPL boundary. Rupture and partial thrombosis of the RAM resulted in mechanical narrowing of the vessel lumen and severe flow limitation, which was further exacerbated by her history of hypertension and hyperlipidemia. This was consistent with the FA findings of delayed filling in the distal parts of the artery. Flow limitation results in decreased blood supply to the retinal capillary plexuses, further decreasing perfusion pressure, causing most disruption to the delicately balanced ICP and DCP blood supply of the middle retinal layer. Middle retinal infarction occurs most readily and presents as PAMM in our patient. In conclusion, we described a novel case of PAMM secondary to a ruptured and partially thrombosed RAM which clearly elucidates the anatomy and physiology of retinal capillary plexuses. [ABSTRACT FROM AUTHOR]

A letter to the editor in response to the article "Macular hemorrhage as a cause of acute angle closure" by G.S. Williams, L. Anderson and D. Eddyshaw in a 2013 issue of the journal is presented.

Purpose: To investigate the posterior and equatorial scleral thickness in patients with autosomal dominant Best disease, a condition that has chronic subretinal fluid., Methods: Retrospective study involving patients with Best disease and age-matched controls. Participants were evaluated with contact B-scan ultrasonography and enhanced depth imaging optical coherence tomography to evaluate scleral thickness in the posterior pole and equator. Univariate analysis and generalized estimating equations were used., Results: Of 9 patients with genetically proven Best disease and 23 age-matched controls, there was no significant difference in the age or the gender proportion between groups. Subfoveal choroidal thickness and axial length were not significantly different between groups. Both posterior scleral (OD; 1.38mm vs. 0.89mm, P<.001 and OS; 1.39mm vs. 0.83mm, P<.001) and equatorial scleral (OD; 0.61mm vs. 0.42mm, P=.003, and OS; 0.55mm vs. 0.41mm, P=.017) thicknesses were much greater in cases as compared with controls. Multivariate analysis showed male sex and having Best disease were each significant predictors of posterior scleral thickness and Best disease was the sole significant predictor for equatorial scleral thickness., Conclusion: BEST1 gene may have a developmental role leading to having a thicker sclera, influencing disease manifestation, and contributing to the accumulation of subretinal fluid in Best disease.

Indocyanine green (ICG) angiography was first approved by the Food and Drug Administration for human use in the 1956. Prior to its use in chorioretinal angiograms, ICG was used to measure blood flow and track cardiac output. It was only in 1969 when two researchers, Kyuga Kogure and Earl Choromokos from the University of Miami, first used ICG to create more accurate angiograms. In the following years, researchers were able to hone the underlying science of this new form of angiography. As time passed and technology advanced, the application of ICG in clinical practice became widespread. Today ICG is used to diagnose and monitor the progression of retinal and choroidal diseases affecting millions of individuals across the globe. ICG utilizes the injection of indocyanine green dye into a patient's bloodstream to visualize abnormalities of the choroid and retina by evaluating choroidal circulation. ICG angiography is useful in the diagnosis and management of occult choroidal neovascularization in age-related macular degeneration and may be used in other inflammatory conditions with central serous chorioretinopathy. ICG angiography offers advanced imaging for improved monitoring and treatment of a wide variety of choroidal and retinal diseases., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Following its implementation in the 1960s, fluorescein angiography (FA) has become a widely used and reliable tool in the diagnosis of retinal and choroidal disorders. FA is an imaging modality utilized to examine the circulation of the retina and choroid. Here, we describe the process of obtaining fundus images with sodium fluorescein dye as a contrast agent. Using this methodology, ophthalmologists may examine the retinal and choroidal vasculature to diagnose a wide scope of retinal and choroidal diseases., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Optical coherence tomography angiography (OCTA) is a noninvasive new imaging modality that can be used to diagnose and monitor progression of retinitis pigmentosa (RP). Cohorts and case series have shown correlation between OCTA findings and visual function and disease severity. Although an early use of the technology is promising, there are concerns about segmentation errors and artifacts. There is also a paucity of data on genotype and how that correlates with OCTA findings. Despite its limitations, OCTA remains a useful tool for clinicians managing retinitis pigmentosa patients., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To evaluate the caliber of the choroidal veins in central serous chorioretinopathy, a disease proposed to be associated with overloading of choroidal venous outflow., Methods: Widefield indocyanine green angiograms of eyes with central serous chorioretinopathy were graded for sausaging defined as three or more contiguous fusiform dilations that vary by at least 50% from the narrowest to largest diameters. A bulbosity was defined as a focal 2X dilation of a blood vessel as compared with the diameter of the surrounding host vessel. The data underwent statistical analysis including the use of generalized estimating equations., Results: There were 73 eyes of 41 patients with a mean age of 53.5 years. Sausaging of vessels was seen in a mean and median of three quadrants per eye. Using generalized estimating equations, the only significant risk factor for sausaging was the use of corticosteroids. The two significant predictors of subfoveal choroidal thickness using generalized estimating equations were age ( P = 0.021) and proportion of quadrants involved by sausaging ( P < 0.001). The decrease in choroidal thickness per year of age was estimated to be 3.7 µ m, while the increase with four quadrant involvement with sausaging was estimated to be 236 µ m. There were a total of 39 bulbosities in 26 eyes (35.6%), preferentially involving intervortex venous anastomoses., Conclusion: Variations in the venous caliber are very common in eyes with central serous chorioretinopathy and seems to be associated with pathophysiologic alterations related to increased pressure within and remodeling of the larger choroidal veins. This may lead to overloading of the choriocapillaris with leakage as one manifestation.

Purpose: To evaluate regional sclera thicknesses as possible risk factors for central serous chorioretinopathy (CSC)., Methods: Patients with CSC and controls were evaluated with contact B-scan ultrasonography using a 20 Mhz concentric phased array ultrasound unit and enhanced depth imaging optical coherence tomography to measure the scleral thickness at the equator and posterior pole. The resultant data were evaluated using univariate analysis and generalized estimating equations., Results: There were 40 patients with CSC with a mean age of 58 years and 23 controls with a mean age of 60.7 years (P = 0.31). The mean subfoveal scleral thicknesses were 1.3 mm in the CSC group and 0.86 mm in the control group (P < 0.001). The mean equatorial scleral thickness was 0.61 mm in the CSC group and 0.42 mm in the control group (P < 0.001). Using generalized estimating equations, the equatorial scleral thickness (P = 0.001), posterior scleral thickness (P < 0.001), and subfoveal choroidal thickness (P = 0.032) were independent predictors of CSC. Once these variables were entered into the equation, neither sex nor age were significant predictors. Generalized estimating equation analysis showed that equatorial, but not posterior, scleral thickness was a significant predictor of subfoveal choroidal thickness., Conclusion: Scleral thicknesses of the posterior and equatorial portions of the eye were found to be significant predictors of CSC, consistent with what was proposed in the theory of venous overload choroidopathy. Direct measurement by high resolution ultrasonography provides independent information about specific regions of the sclera and also avoids making speculative assumptions derived from anterior segment measurements.

Purpose: The purpose of this study was to describe the characteristics of polypoidal choroidal vasculopathy (PCV) subtypes among patients from a multicenter randomized controlled trial and to determine the impact of PCV subtypes on clinical outcomes., Methods: This was a prospective cohort study of 61 patients with macular PCV from the EVEREST study. Indocyanine green (ICGA) and fluorescein angiography (FA) obtained using standardized imaging protocols were graded to classify PCV into three subtypes. Type A PCV had polyps with interconnecting channels, type B had polyps with branching vascular networks, but no significant leakage on FA, and type C had polyps with branching vascular networks and leakage on FA. The best-corrected visual acuity (BCVA) and proportion of patients with BCVA ≥ 20/40 were compared among the three PCV subtypes., Results: Of the 61 patients, 54 were gradable for PCV subtype. Among these, 8 had type A PCV (14.8%), 27 had type B (50%), and 19 had type C (35.2%). At baseline, BCVA was 67.1 letters for type A, 58.7 for type B, and 43.5 for type C (P < 0.001). At 6 months, BCVA was highest among patients with type A compared with types B and C (80.1 letters versus 67.2 versus 50.4, respectively; P < 0.001). Type A PCV gained 13 letters compared with 8.5 (type B) and 6.9 (type C). BCVA ≥ 20/40 was highest for type A compared with types B and C (100% vs. 51.9% vs. 10.5%; P < 0.001). On performing ANCOVA, PCV subtype and baseline BCVA significantly affected final BCVA., Conclusions: The visual outcome following treatment varies with PCV subtype classification. The distinction in clinical outcomes between the PCV subtypes is observed in the initial months following the start of treatment.

Background and Objective: To compare retinal thicknesses measured using swept-source optical coherence tomography (SS-OCT) and spectral-domain (SD) OCT devices., Patients and Methods: In a cohort study of 76 healthy eyes and 21 eyes with high myopia, mean retinal thicknesses in ETDRS subfields were compared between OCT scans obtained from the Topcon DRI OCT-1 (Topcon, Tokyo, Japan), Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany), and Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA)., Results: Central retinal thickness measurements differed significantly among the three OCT devices (Spectralis: 271 µm; Cirrus: 254 µm; DRI OCT-1: 238 µm; P < .001), with mean differences ranging from 15.6 µm to 37 µm. Intraclass correlation coefficients were at least 0.94 for any pair of machines. Similar results were observed in all nine ETDRS subfields. In all sectors, retinal thickness measurements obtained using the 3-D and radial scans of the SS-OCT were similar (mean differences: 0.7 to 3.8 µm)., Conclusion: Retinal thickness measurements obtained from DRI OCT-1 and SD-OCT are different and should be accounted for when comparing results of OCT scans from different devices., (Copyright 2015, SLACK Incorporated.)