Should clinical automated perimetry be considered for routine functional assessment of early/intermediate age-related macular degeneration (AMD)? A systematic review of current literature.

PURPOSE: There is growing interest in functional testing for early/intermediate age-related macular degeneration (iAMD). However, systematic evaluation of existing clinical functional tests is lacking. This systematic review examines evidence for using clinical automated perimetry in routine assessment of early/iAMD. RECENT FINDINGS: PubMed, Web of Science Core Collection, and Embase were searched from inception to October 2020 to answer, is there evidence of visual field defects in early/iAMD, and if so, are early/iAMD visual field defects linked to real-world patient outcomes? Articles using clinical automated perimetry (commercially accessible and non-modified devices/protocols) were included. Microperimetry was excluded as this has yet to be incorporated into clinical guidelines. The primary outcome was global visual field indices including mean deviation (MD), pattern standard deviation (PSD), mean sensitivity (MS) and frequency of defects. The secondary outcome was any real-world patient outcome including quality of life and/or activities of daily living indices. Twenty-six studies were eligible for inclusion and all studies were observational. There was consistent evidence of worsened MD, PSD, MS and frequency of defects for early/iAMD compared to normal eyes under photopic, low-photopic and scotopic conditions. Meta-analysis of studies using standard automated perimetry (SAP) under photopic conditions revealed worsened MD (-1.52dB [-2.27, -0.78 dB]) and MS (-1.47dB [-2, -0.94 dB]) in early/iAMD compared to normal eyes, representing large statistical effect sizes but non-clinically meaningful reductions. There was insufficient data for meta-analyses regarding other clinical automated perimetry protocols. Only one study assessed a real-world patient outcome (on-road driving performance), with no significant link to visual field outcomes in early/iAMD. SUMMARY: Significant reduction of global visual field indices is present in early/iAMD, but not clinically meaningful using SAP under photopic conditions. Translational relevance of visual field outcomes to patient outcomes in early/iAMD remains unclear. Thus, SAP under photopic conditions is unlikely to be useful for routine assessment of early/iAMD.

Vinpocetine protects inner retinal neurons with functional NMDA glutamate receptors against retinal ischemia.

Retinal ischemia is involved in the pathogenesis of many major vision threatening diseases. Vinpocetine is a natural drug, which has a range of neuroprotective actions against retinal ischemia including modulating cation flow, improving metabolic activity and preventing apoptosis. The exact mechanism behind these actions remains unknown but may involve glutamate receptors, major components of the ischemic cascade. This study examined the effects of vinpocetine in association with specific ionotropic glutamate receptor agonists: N-methyl-D-aspartate (NMDA) and kainate. Vinpocetine's actions to improve cation channel permeability and cell marker immunoreactivity following ischemia appeared to be limited to NMDA activation with no changes observed following kainate stimulation. Vinpocetine's actions were lost in the presence of an NMDA receptor inhibitor further suggesting they may be secondary to NMDA receptor activation. NMDA receptor function was also necessary for vinpocetine's actions on glucose availability during ischemia but not lactate dehydrogenase (LDH) activity in the ischemic retina suggesting not all of vinpocetine's actions are linked to NMDA receptor function. These results may explain vinpocetine's effectiveness as a neuroprotective agent as the NMDA receptor is implicated in the pathogenesis of ischemia in a range of tissues of the central nervous system.

Retinal Thickness Changes throughout the Natural History of Drusen in Age-related Macular Degeneration.

SIGNIFICANCE: Drusen are associated with retinal thinning in age-related macular degeneration (AMD). These changes, however, have mostly been examined at single time points, ignoring the evolution of drusen from emergence to regression. Understanding the full breadth of retinal changes associated with drusen will improve understanding of disease pathogenesis. PURPOSE: The purpose of this study was to assess how the natural history of drusen affects retinal thickness, focusing on the photoreceptor and retinal pigment epithelium (RPE) layers. METHODS: Spectral domain optical coherence tomography of subjects with intermediate AMD (n = 50) who attended the Centre for Eye Health, Sydney, Australia, for two separate visits (476 ± 16 days between visits) was extracted. Scans were automatically segmented with manufacturer software then assessed for drusen that had emerged, grown, or regressed between visits. For each identified lesion, the thickness of each retinal layer at the drusen peak and at adjacent drusen-free areas (150 µm nasal and temporal to the druse) was compared between visits. RESULTS: Before drusen emergence, the RPE was significantly thicker at the drusen site (14.2 ± 2.6%) compared with neighboring drusen-free areas. There was a 71% sensitivity of RPE thickening predicting drusen emergence. Once drusen emerged, significant thinning of all outer retinal layers was observed, consistent with previous studies. Drusen growth was significantly correlated with thinning of the outer retina (r = -0.38, P < .001). Drusen regression resulted in outer retinal layers returning to thicknesses not significantly different from baseline. CONCLUSIONS: The natural history of drusen is associated with RPE thickening before drusen emergence, thinning of the outer nuclear layer as well as photoreceptor and RPE layers proportional to drusen growth, and return to baseline thickness after drusen regression. These findings have useful clinical applications, providing a potential marker for predicting drusen emergence for AMD prognostic and intervention studies and highlighting that areas of normal retinal thickness in AMD may be former sites of regressed drusen.

Peripheral retinal findings in populations with macular disease are similar to healthy eyes.

PURPOSE: Recent evidence suggests several macular diseases are associated with peripheral retinal changes. This study investigated the number, type and management consequences of peripheral retinal findings detected in patients attending a referral only, eye-care clinic, the Centre for Eye Health(CFEH) with macular disease. METHODS: Records of 537 patients attending CFEH for a macular assessment were included in the study. Subjects were classified as having age-related macular degeneration (AMD), epiretinal membrane (ERM), central serous chorioretinopathy (CSCR), inherited macular dystrophy or no macular disease. Data extracted included reason for referral, macular findings, peripheral findings (based on examination by ultra-widefield scanning laser ophthalmoscopy), diagnosis and management. RESULTS: After age-matching, the number of peripheral findings in subjects with AMD, ERM or CSCR was not significant different to normal subjects. The most common finding for all cohorts were non-specific, degenerative changes such as drusen or pigmentation (61-72%) except inherited macular dystrophy subjects who had mostly vascular findings (30%; p < 0.05). Subjects with AMD and ERM with peripheral findings were significantly more likely to be reviewed or referred to an ophthalmologist than discharged back to their community eye care provider compared to subjects without findings. However only 8% of subjects had altered management based specifically on peripheral findings suggesting the macular findings in most subjects dictated their management. For those with a change, it was significant (upgrade to referral to an ophthalmologist). Peripheral findings also flagged 5% of subjects with vascular findings for referral to their general practitioner (GP). CONCLUSIONS: Overall, the percentage and distribution of peripheral retinal findings in some macular diseases was similar to normal subjects. However, subjects with peripheral findings appeared to have significant differences in management. Considering some common findings, such as peripheral drusen may be relevant to AMD pathogenesis and therefore affect management of this disease, assessment of the peripheral retina should not be overlooked when the clinical focus is on the posterior pole.

Pre-treatment with vinpocetine protects against retinal ischemia.

Vinpocetine has been shown to have beneficial effects for tissues of the central nervous system subjected to ischemia and other related metabolic insults. We recently showed vinpocetine promotes glucose availability, prevents unregulated cation channel permeability and regulates glial reactivity when present during retinal ischemia. Less is known however about the ability of vinpocetine to protect against future ischemic insults. This study explores the effect of vinpocetine when used as a pre-treatment in an ex vivo model for retinal ischemia using cation channel permeability of agmatine (AGB) combined with immunohistochemistry as a measure for cell functionality. We found that vinpocetine pre-treatment reduced cation channel permeability and apoptotic marker immunoreactivity in the GCL and increased parvalbumin immunoreactivity of inner retinal neurons in the inner nuclear layer following ischemic insult. Vinpocetine pre-treatment also reduced Müller cell reactivity following ischemic insults of up to 120 min compared to untreated controls. Many of vinpocetine's effects however were transient in nature suggesting the drug can protect retinal neurons against future ischemic damage but may have limited long-term applications.

Fundus Autofluorescence in Age-related Macular Degeneration.

: Fundus autofluorescence (FAF) provides detailed insight into the health of the retinal pigment epithelium (RPE). This is highly valuable in age-related macular degeneration (AMD) as RPE damage is a hallmark of the disease. The purpose of this paper is to critically appraise current clinical descriptions regarding the appearance of AMD using FAF and to integrate these findings into a chair-side reference. A wide variety of FAF patterns have been described in AMD, which is consistent with the clinical heterogeneity of the disease. In particular, FAF imaging in early to intermediate AMD has the capacity to reveal RPE alterations in areas that appear normal on funduscopy, which aids in the stratification of cases and may have visually significant prognostic implications. It can assist in differential diagnoses and also represents a reliable, sensitive method for distinguishing reticular pseudodrusen. FAF is especially valuable in the detection, evaluation, and monitoring of geographic atrophy and has been used as an endpoint in clinical trials. In neovascular AMD, FAF reveals distinct patterns of classic choroidal neovascularization noninvasively and may be especially useful for determining which eyes are likely to benefit from therapeutic intervention. FAF represents a rapid, effective, noninvasive imaging method that has been underutilized, and incorporation into the routine assessment of AMD cases should be considered. However, the practicing clinician should also be aware of the limitations of the modality, such as in the detection of foveal involvement and in the distinction of phenotypes (hypo-autofluorescent drusen from small areas of geographic atrophy).

The advantages of intermediate-tier, inter-optometric referral of low risk pigmented lesions.

PURPOSE: Pigmented ocular lesions are commonly encountered by eye-care professionals, and range from benign to sight or life-threatening. After identifying a lesion, the primary care professional must establish the likely diagnosis and decide either to reassure, to monitor or to refer. The increasing use of ocular imaging technologies has contributed to an increase in the detection rate of pigmented lesions and a higher number of referrals, which may challenge existing pathways of health-care delivery. Specialist services may be over-burdened by referring all patients with pigmented lesions for an opinion, while inter-optometric referrals are underutilised. The aim of this study was to describe the referral patterns of pigmented lesions to an optometry led intermediate-tier collaborative care clinic. METHODS: We performed a retrospective review of patient records using the list of patients examined at Centre for Eye Health (CFEH) for an initial or follow up pigmented lesion assessment between the 1/7/2013 and the 30/6/2016. Analysis was performed on: patient demographic characteristics, the referrer's tentative diagnosis, CFEH diagnosis and recommended management plan. RESULTS: Across 182 patient records, the primary lesion prompting referral was usually located in the posterior segment: choroidal naevus (105/182, 58%), congenital hypertrophy of the retinal pigment epithelium (CHRPE; 11/182, 6%), chorioretinal scarring (10/182, 5%) or not specified (52/182, 29%). Referrals described a specific request for ocular imaging in 25 instances (14%). The number of cases with a non-specific diagnosis was reduced after intermediate-tier care assessment (from 29% to 10%), while the number of diagnoses with less common conditions rose (from 2% to 21%). There was a 2% false positive referral rate to intermediate-tier care and a first visit discharge rate of 35%. A minority required on-referral to an ophthalmologist (22/182, 12%), either for unrelated incidental ocular findings, or suspicious choroidal naevi. Conditions most amenable to optometric follow up included: 1) chorioretinal scarring, 2) choroidal naevus, and 3) CHRPE. CONCLUSIONS: Intermediate-tier optometric eye-care in pigmented lesions (following opportunistic primary care screening) has the potential to reduce the number of cases with non-specific diagnoses and to increase those with less common diagnoses. The majority of cases seen under this intermediate-tier model required only ongoing optometric surveillance.

Macromolecular markers in normal human retina and applications to human retinal disease.

Macromolecular cell markers are essential for the classification and characterization of the highly complex and cellularly diverse vertebrate retina. Although a plethora of markers are described in the current literature, the immunoreactivity of these markers in normal human tissue has not been fully determined. This is problematic as they are quintessential to the characterization of morphological changes associated with human retinal disease. This review provides an overview of the macromolecular markers currently available to assess human retinal cell types. We draw on immunohistochemical studies conducted in our laboratories to describe marker immunoreactivity in human retina alongside comparative descriptions in non-human tissues. Considering the growing number of eye banks services offering healthy and diseased human retinal tissue, this review provides a point of reference for future human retina studies and highlights key species specific disease applications of some macromolecular markers.

Infrared reflectance imaging in age-related macular degeneration.

PURPOSE: The purpose of this article is to describe the appearance of age-related macular degeneration (AMD) phenotypes using infrared (IR) reflectance imaging. IR reflectance imaging of the retina has the potential to highlight specific sub-retinal features and pathology. However, its role in macular disease, specifically AMD, is often underestimated and requires clarification. RECENT FINDINGS: Recent advances in clinical methods, imaging and scientific knowledge may be integrated to improve the accuracy of disease stratification in AMD. In particular, IR imaging holds an underutilised sensitivity to detect reticular pseudodrusen, which have been repeatedly described as a high-risk sign for late AMD. SUMMARY: This article provides clinically relevant descriptions of AMD phenotypes using IR reflectance imaging. The findings are integrated with images from cases seen at the Centre for Eye Health. As primary eye-care providers assume a critical role in the detection, diagnosis and management of AMD, we also provide a chair-side reference to assist clinicians in interpreting IR images in AMD.

Collaborative care of non-urgent macular disease: a study of inter-optometric referrals.

PURPOSE: Diseases involving the macula and posterior pole are leading causes of visual impairment and blindness worldwide and may require prompt ophthalmological care. However, access to eye-care and timely patient management may be limited due to inefficient and inappropriate referrals between primary eye-care providers and ophthalmology. Optometrists with a special interest in macular disease may be useful as a community aid to better stratify and recommend best-practice management plans for suitable patients. This study assesses such a notion by appraising the optometric referral patterns of patients with suspected macular disease to an intermediate-tier optometric imaging clinic. METHODS: We performed a retrospective review of patient records and referrals using patients examined at Centre for Eye Health (CFEH) for an initial or follow up macular assessment between the 1/7/2013 and 30/6/2014 (n = 291). The following data were analysed: patient demographic characteristics, primary reason for referral, diagnosed/suspected condition, CFEH diagnosis and recommended management plan. RESULTS: The number of referrals stipulating a diagnosis, confirmed after evaluation at CFEH was 121 of 291 (42%). After evaluation at CFEH, the number of cases without a specific diagnosis was approximately halved (reduced from 47% to 23%), while the number of cases with no apparent defect or normal aging changes rose from 1% to 15%. Overall diagnostic congruency for specified macular conditions was high (58-94%); cases were seldom (30/291, 10%) found to have a completely different macular condition. 244 of 291 (84%) patients seen at CFEH were recommended ongoing optometric care: either with the referring optometrist or through recall to CFEH. Referral to an ophthalmologist was recommended in 47 instances (16%). CONCLUSIONS: More widespread adoption of intermediate-tier optometric eye-care referral pathways in macular disease (following opportunistic primary care screening) has the potential to reduce the number of cases with non-specific diagnoses and to increase those with a diagnosis of normal aging changes or no apparent disease. The majority of cases seen under this intermediate-tier model required ongoing optometric care only and did not require face-to-face consultation with an ophthalmologist.

Vinpocetine modulates metabolic activity and function during retinal ischemia.

Vinpocetine protects against a range of degenerative conditions and insults of the central nervous system via multiple modes of action. Little is known, however, of its effects on metabolism. This may be highly relevant, as vinpocetine is highly protective against ischemia, a process that inhibits normal metabolic function. This study uses the ischemic retina as a model to characterize vinpocetine's effects on metabolism. Vinpocetine reduced the metabolic demand of the retina following ex vivo hypoxia and ischemia to normal levels based on lactate dehydrogenase activity. Vinpocetine delivered similar effects in an in vivo model of retinal ischemia-reperfusion, possibly through increasing glucose availability. Vinpocetine's effects on glucose also appeared to improve glutamate homeostasis in ischemic Müller cells. Other actions of vinpocetine following ischemia-reperfusion, such as reduced cell death and improved retinal function, were possibly a combination of the drug's actions on metabolism and other retinal pathways. Vinpocetine's metabolic effects appeared independent of its other known actions in ischemia, as it recovered retinal function in a separate metabolic model where the glutamate-to-glutamine metabolic pathway was inhibited in Müller cells. The results of this study indicate that vinpocetine mediates ischemic damage partly through altered metabolism and has potential beneficial effects as a treatment for ischemia of neuronal tissues.

OCT and Fundus Autofluorescence Enhances Visualization of White Dot Syndromes.

PURPOSE: White dot syndromes (WDS) are a group of inflammatory conditions characterized by white lesions at the retina and choroid level. Detection and monitoring of these syndromes are currently hampered by the subtlety of these lesions, making them difficult to image using traditional clinical techniques. New imaging modalities such as optical coherence tomography (OCT) and fundus autofluorescence (FAF) offer new opportunities for clinicians to noninvasively image WDS. METHODS: A literature search was performed using a variety of WDS as the search terms. All articles from January 2004 to May 2014 were analyzed for clinical information regarding imaging of the diseases using OCT or FAF. RESULTS: Current descriptions of OCT and FAF imaging of WDS are fragmented across case reports and small-scale studies. Assessing clinical presentation of WDS using OCT and FAF, however, is useful as the retinal layers affected in these syndromes are well characterized by these technologies. Furthermore, the new information revealed by OCT and FAF is helpful to elucidate the underlying mechanisms of these diseases in combination with known clinical and angiographic findings. CONCLUSIONS: This review collates current literature and provides a succinct overview of the clinical presentation of WDS using OCT and FAF.

Pigmented Lesions of the Retinal Pigment Epithelium.

: The primary eye care practitioner assumes an important role in clinical decisions involving the differentiation between malignant and nonmalignant pigmented lesions. A misdiagnosis may have profound consequences on patient management and visual or life prognosis. However, information on these lesions, particularly their appearance using advanced imaging, is fragmented throughout the literature. The purpose of this review is to describe these features in detail, so that the implications of this information on clinical practice are more readily apparent. Clinically relevant descriptions of pigmented lesions of the retinal pigment epithelium using traditional and advanced imaging modalities in the literature were collated and integrated with findings from patients seen at the Centre for Eye Health. The information was then organized and tabulated. Finally, a flow diagram was created to be used as a clinical reference in the differential diagnosis of pigmented lesions of the retinal pigment epithelium.

Atypical Features of Fuchs Uveitis Syndrome.

PURPOSE: To review the atypical features of Fuchs uveitis syndrome. METHODS: A retrospective review of records of a private optometric practice of patients with diagnosed Fuchs uveitis syndrome was performed. RESULTS: Three atypical cases of Fuchs uveitis syndrome are presented. Patient 1 is a patient who required the use of topical corticosteroids to alleviate acute symptoms of uveitis. Patient 2 is a patient who presented at a very young age with aggressive Fuchs uveitis and who subsequently developed secondary open-angle glaucoma. Patient 3 presented with primary open-angle glaucoma, was treated with topical ocular hypotensive medications, but then subsequently presented with manifest Fuchs uveitis syndrome in the affected eye. Patient 3 was treated with topical prostaglandin analogs among other medical therapies. CONCLUSIONS: Fuchs uveitis syndrome has a diverse clinical spectrum. It is a syndrome that is diagnosed using a constellation of clinical signs. However, some cases may present atypically and clinicians should be prepared to use less conventional therapies such as topical corticosteroids and prostaglandin analogs in the treatment of acute uveitic attacks and secondary open-angle glaucoma, respectively.

Sildenafil alters retinal function in mouse carriers of retinitis pigmentosa.

Sildenafil, the active ingredient in Viagra, has been reported to cause transient visual disturbance from inhibition of phosphodiesterase 6 (PDE6), a key enzyme in the visual phototransduction pathway. This study investigated the effects of sildenafil on the rd1(+/-) mouse, a model for carriers of Retinitis Pigmentosa which exhibit normal vision but may have a lower threshold for cellular stress caused by sildenafil due to a heterozygous mutation in PDE6. Sildenafil caused a dose-dependent decrease in electroretinogram (ERG) responses of normal mice which mostly recovered two days post administration. In contrast, rd1(+/-) mice exhibited a significantly reduced photoreceptor and a supernormal bipolar cell response to sildenafil within 1 h of treatment. Carrier mice retinae took two weeks to return to baseline levels suggesting sildenafil has direct effects on both the inner and outer retina and these effects differ significantly between normal and carrier mice. Anatomically, an increase in expression of the early apoptotic marker, cytochrome C in rd1(+/-) mice indicated that the effects of sildenafil on visual function may lead to degeneration. The results of this study are significant considering approximately 1 in 50 people are likely to be carriers of recessive traits leading to retinal degeneration.

Age-related macular degeneration: linking clinical presentation to pathology.

Age-related macular degeneration (AMD) is one of the leading causes of blindness worldwide in the elderly population. Optometrists, as primary eye health care providers, require the skills and knowledge to accurately diagnose and manage AMD patients. There is an overwhelming body of research related to the clinical presentation, etiology, epidemiology, and pathology of this disease. Additionally, the evolution of new imaging modalities creates new opportunities to clinically detect and analyze previously uncharacterized and earlier changes in the retina. The challenge for optometrists is to combine all this information into an applicable knowledge base for use in everyday clinical assessment of AMD so that timely and accurate referrals can be made to retinal specialists. This review attempts to address this issue by linking the clinical presentation of AMD with the underlying disease biology. We emphasize the contribution of recent noninvasive imaging technologies to the clinical assessment of early and more advanced AMD including optical coherence tomography, fundus autofluorescence, and infrared reflectance.

Retinal vessel diameters in intermediate age-related macular degeneration using en face optical coherence tomography.

CLINICAL RELEVANCE: Clinical assessment of age-related macular degeneration (AMD) relies on biomarkers that do not necessarily reflect the contributions of vascular dysfunction. Validation of clinically accessible methods of measuring retinal vascular integrity could provide a more holistic understanding of AMD-related changes to facilitate appropriate care. BACKGROUND: There is conflicting evidence if retinal vessel calibre is significantly altered in the early stages of AMD. This study examined the outer and inner diameters of first order retinal vessels in intermediate AMD eyes using en face optical coherence tomography (OCT). METHODS: Retinal en face (6 × 6 mm) OCT images were examined in a single eye of participants with intermediate AMD (n = 46) versus normal macula (n = 43) for arterioles (all identifiable) and venules (40/46 and 39/43 identifiable). All participants were aged ≥50 years without diabetes mellitus, hypertension, or other systemic vascular disease. RESULTS: Intra- and inter-grader agreement was good-to-excellent for all en face OCT measurements of arteriole and venule diameters (intraclass correlation coefficient = 0.87 to 0.99). Arteriolar outer diameters (82.3 ± 19.8 µm vs 73.8 ± 16.1 µm; p < 0.05) and inner diameters (35.1 ± 8.4 µm vs 31.5 ± 8.1 µm; p < 0.05) were significantly greater in AMD eyes compared to normal eyes. Venular inner diameter was significantly greater (43.1 ± 9.5 µm vs 39.2 ± 10.1 µm; p < 0.05), but outer diameter remained unchanged (p = 0.17) in AMD eyes compared to normal eyes. CONCLUSION: Arteriolar dilation and altered venular inner diameter were observed in intermediate AMD eyes. These results support further investigation of vascular contributions to AMD in the early stages of disease, possibly using the en face OCT imaging modality.

Spatial Analysis Reveals Vascular Changes in Retinal and Choroidal Vessel Perfusion in Intermediate AMD With Reticular Pseudodrusen.

Purpose: To examine the effect of reticular pseudodrusen (RPD) on retinal and choroidal vessel perfusion (VP) topography in intermediate age-related macular degeneration (iAMD) using refined spatial analyses. Methods: This was a retrospective cross-sectional study of 120 individuals with 30 iAMDRPD, 60 iAMDno_RPD, and 30 normal eyes, propensity-score matched by age, sex, and presence of cardiovascular-related disease. VP of the superficial and deep retinal and choriocapillaris vascular slabs was assessed from 6 × 6-mm optical coherence tomography angiography (OCTA) scans divided into 126 × 126 grids, with adjustment for various person- and eye-level factors. Grid-wise VP differences (%) among the groups were spatially assessed according to analyses based on the Early Treatment for Diabetic Retinopathy Study (ETDRS), eccentricity (µm), and degree (°). Results: VP was significantly decreased between iAMDRPD and iAMDno_RPD, across all vascular slabs in various ETDRS sectors (up to -2.16%; 95% confidence interval, -2.99 to -1.34; P < 0.05). Eccentricity analyses revealed more complex patterns: a bisegmented relationship where VP in iAMDRPD eyes decreased linearly toward 1000 µm then returned toward similar values as iAMDno_RPD, plateauing around 2000 µm in the superficial and 3000 µm in the deep retina (R2 = 0.57-0.9; P < 0.001). Degree-based analysis further showed that the greatest VP differences in iAMDRPD eyes were commonly located superiorly and nasally across all vascular slabs (P < 0.05). Conclusions: RPD appears to compound the vascular impact of iAMD, displaying complex spatial patterns beyond the ETDRS sectors. This highlights the importance of considering spatial delineations for future work regarding the role of RPD and vascular dysfunction.

OCTA Signal Quality Augmentation Using the Isometric Handgrip Test to Maximize Vascular Flow (SQUEEZE): A Randomized Crossover Trial.

Purpose: To determine if performing the isometric handgrip test (IHGT) can augment optical coherence tomography angiography (OCTA) vascular signal quality in eyes with macular abnormalities. Methods: A randomized, single-blinded crossover trial was conducted including 36 participants with macular abnormalities, randomized to undergo OCTA with or without the IHGT, then crossed over to the alternate "intervention" after 1 minute. The primary outcome was OCTA signal quality after 1 minute of squeezing at 50% maximum grip strength. Secondary outcomes were other measures of vascular flow and systemic blood pressure (BP), also regressed against person- and eye-level covariables. Results: Primary analysis of OCTA signal quality with versus without the IHGT was nonsignificant (P = 0.73). Nested analyses showed that the IHGT resulted in increased OCTA B-scan retinal vascular flow signal (2.95 [-1.64 to 7.55] Δ%, P < 0.05) and increased systolic BP, diastolic BP, pulse pressure, and mean arterial pressure (4.94 [0.41 to 9.47] to 12.38 [8.01 to 16.75] mm Hg, P < 0.05). OCTA signal quality and en face vessel density and perfusion changes were associated with sex, refraction, race/ethnicity, and right-hand IHGT use (P < 0.05). Greater increases in systolic and diastolic BP and mean arterial pressure were generally associated with right-hand IHGT use and greater maximum grip strength (P < 0.09). Conclusions: The IHGT can temporarily increase OCTA B-scan retinal vascular flow signal in participants with macular abnormalities. IHGT-induced changes to systemic BP appear to be linked to absolute (rather than relative) grip strength, implying that the IHGT may be ineffective with low grip strength. Further research in larger populations is warranted. Translational Relevance: This study provides early validation that the IHGT may augment OCTA output, which may lead to improved noninvasive detection of pathologic vascular changes.

Retinal sensitivity changes in early/intermediate AMD: a systematic review and meta-analysis of visual field testing under mesopic and scotopic lighting.

Visual fields under mesopic and scotopic lighting are increasingly being used for macular functional assessment. This review evaluates its statistical significance and clinical relevance, and the optimal testing protocol for early/intermediate age-related macular degeneration (AMD). PubMed and Embase were searched from inception to 14/05/2022. All quality assessments were performed according to GRADE guidelines. The primary outcome was global mean sensitivity (MS), further meta-analysed by: AMD classification scheme, device, test pattern, mesopic/scotopic lighting, stimuli size/chromaticity, pupil dilation, testing radius (area), background luminance, adaptation time, AMD severity, reticular pseudodrusen presence, and follow-up visit. From 1489 studies screened, 42 observational study results contributed to the primary meta-analysis. Supported by moderate GRADE certainty of the evidence, global MS was significantly reduced across all devices under mesopic and scotopic lighting with large effect size (-0.9 [-1.04, -0.75] Hedge's g, P < 0.0001). The device (P < 0.01) and lighting (P < 0.05) used were the only modifiable factors affecting global MS, whereby the mesopic MP-1 and MAIA produced the largest effect sizes and exceeded test-retest variabilities. Global MS was significantly affected by AMD severity (intermediate versus early AMD; -0.58 [-0.88, -0.29] Hedge's g or -2.55 [3.62, -1.47] MAIA-dB) and at follow-up visit (versus baseline; -0.62 [-0.84, -0.41] Hedge's g or -1.61[-2.69, -0.54] MAIA-dB). Magnitudes of retinal sensitivity changes in early/intermediate AMD are clinically relevant for the MP-1 and MAIA devices under mesopic lighting within the central 10° radius. Other factors including pupil dilation and dark adaptation did not significantly affect global MS in early/intermediate AMD.