Purpose Two‐colour computerised perimetry is a technique developed for assessing cone‐ and rod‐function at fixed background luminances in retinal disease. However, the state of adaptation during testing is unknown but crucial in the interpretation of results. We therefore aimed to determine the adaptational state of rod‐ and cone‐mechanisms in two‐colour perimetry. Methods Sensitivity to 480 nm (blue) and 640 nm (red) Goldmann size V targets was determined for 10 normal subjects aged 16 to 46 years at 17 locations in the central 60 degrees of the visual field under scotopic conditions and then from −1.5 log cd m−2 to 2 log cd m−2 (white background) in 0.5 log unit steps. Data were fitted with threshold versus intensity (tvi) functions of the form logT = logT0 + log ((A + A0)/A0)n. Results No clear rod‐cone break was observed for 640 nm stimuli. For 480 nm stimuli, transition from rod‐detection to cone‐detection occurred at mesopic illumination levels, where rod adaptation approached Weber behaviour. Cone detection mechanisms did not display Weber‐like adaptation until the background luminance approached 1 log cd.m−2. Diseases resulting in a “filter effect” ‐ including disorders of the photoreceptors ‐ are therefore predicted to affect sensitivity when rod function is probed with short‐wavelength targets under scotopic conditions, but less so under mesopic conditions. Filter effects are similarly anticipated to affect cone function measured using long‐wavelength targets under mesopic conditions (e.g., during microperimetry), but less so under photopic conditions. Conclusions Asymmetries in adaptation in automated two‐colour perimetry are predicted to artefactually favour the detection of losses in rod sensitivity under scotopic conditions and cones under mesopic conditions.

Purpose: To characterize dark adaptation in patients with pseudoxanthoma elasticum, a systemic disease leading to calcification of elastic tissue including the Bruch membrane. Methods: In this prospective case–control study, dark adaptation thresholds were measured using a Goldmann-Weekers dark adaptometer. Additional assessments included best-corrected visual acuity testing, contrast sensitivity, low luminance deficit, and vision-related quality of life. Results: Dark adaptation thresholds were significantly higher, and adaptation periods were prolonged in patients with pseudoxanthoma elasticum (n = 35; 33 with 2 ABCC6 mutations) compared with controls (n = 35). The time to adapt 4 log units (20.6 ± 8.6 vs. 8.0 ± 1.3 minutes) and the mean dark adaptation threshold after 15 minutes (3.5 ± 1.1 vs. 1.8 ± 0.2 log units) were significantly different between patients and controls (both P < 0.001). Low luminance deficits (12.3 ± 6.4 vs. 6.1 ± 4.3 ETDRS letters), contrast sensitivity (1.4 ± 0.3 vs. 1.9 ± 0.1), and low luminance-related quality of life (LLQ score: 1,286 ± 355 vs. 2,167 ± 68) were also significantly worse in patients with pseudoxanthoma elasticum (all, P < 0.001). Two patients were treated with high-dose vitamin A which partially reversed impaired dark adaptation. Conclusion: Patients with pseudoxanthoma elasticum often have impaired dark adaptation. Positive effects of vitamin A supplementation may indicate restricted retinal access of vitamin A through the Bruch membrane as one possible underlying pathogenic factor.

spectrum of the foveal configuration and foveal avascular zone in patients with Alport syndrome. Invest Ophthalmol Vis Sci. 2020;61(2):5. https://doi.org/10.1167/iovs.61.2.5 PURPOSE.To investigate characteristics of the foveal pit and the foveal avascular zone (FAZ) in patients with Alport syndrome (AS), a rare monogenetic disease due to mutations in genes encoding for collagen type IV. METHODS.Twenty-eight eyes of nine patients with AS, and five autosomal-recessive carriers and 15 eyes from 15 age-similar healthy control subjects were examined using optical coherence tomography (OCT) and OCT-angiography (OCT-A). Foveal configuration and FAZ measures including the FAZ area, circularity, and vessel density in the central 1°and 3°were correlated. RESULTS.Foveal hypoplasia was found in 10 eyes from seven patients with either genotype. In contrast, a staircase foveopathy was found in seven eyes of four X-linked AS patients. The average FAZ area did not differ significantly between AS patients and control subjects (mean ± SD 0.24 ± 0.24 mm 2 vs. 0.21 ± 0.09 mm 2 ; P = 0.64). Five eyes showed absence or severe anomalies of the FAZ with crossing macular capillaries that was linked to the degree of foveal hypoplasia on OCT images leading to a significant inverse correlation of FAZ area and foveal thickness (r = −0.88; P < 0.001). In contrary, female patients with X-linked mutations exhibited a significantly greater FAZ area (0.48 ± 0.30 mm 2 vs. 0.21 ± 0.09 mm 2 ; P = 0.007), in line with OCT findings of a staircase foveopathy. CONCLUSIONS.The foveal phenotypic spectrum in AS ranges from foveal hypoplasia and absence of a FAZ to staircase foveopathy with an enlarged FAZ. Because the development of the FAZ and foveal pit are closely related, these findings suggest an important role for collagen type IV in foveal development and maturation.

Purpose: To define, characterize, and classify hyperreflectivity on optical coherence tomography and report its prevalence in macular telangiectasia Type 2.Methods: In a primary cross-sectional analysis, multimodal imaging data were retrospectively analyzed. The definition of hyperreflectivity and neovascularization on optical coherence tomography followed optical coherence tomography angiographybased criteria. Eyes were graded for the presence of hyperreflectivity and neovascularization and further categorized into three classes based on position and extent of hyperreflectivity. In a secondary analysis, eyes were reviewed for $24 months using optical coherence tomography imaging.Results: Three hundred and twenty-two eyes from 161 patients were analyzed in the cross-sectional analysis. Hyperreflectivity was found in 177 (55%) and neovascular membranes in 49 (15%) eyes. Hyperreflectivity correlated significantly with parameters indicative of disease progression. In the longitudinal analysis, 206 eyes from 103 patients were reviewed over a mean of 35.6 months. 17/86 eyes (20%) showed a de novo development of hyperreflectivity. 8/29 eyes (28%) with preexistent intraretinal hyperreflectivity developed outer retinal hyperreflectivity. A high proportion of eyes with outer retinal hyperreflectivity (17/52 [33%]) developed neovascular membranes.Conclusion: Hyperreflectivity represents a common finding in macular telangiectasia Type 2 but lacks a uniform definition. We propose a hyperreflectivity grading scale that may help to estimate disease progression and identify eyes at risk for developing neovascular membranes.

Dermatofibrosarcoma protuberans (DFSP) is a fibroblastic tumor characterized by a high rate of recurrence following conventional surgical treatment. Several different histopathologic patterns exist, with the "cartwheel" pattern the most common. In this report, a patient with the unusual myxoid histopathologic pattern was successfully treated with Mohs surgery.

IMPORTANCECorrelates for Bruch membrane alterations are needed for interventional trials targeting the Bruch membrane in pseudoxanthoma elasticum (PXE).OBJECTIVES To quantify mesopic and scotopic light sensitivity and identify its microstructural correlates associated with a diseased Bruch membrane in patients with PXE. DESIGN, SETTING, AND PARTICIPANTSA prospective, single-center, cross-sectional case-control study was conducted at a tertiary referral center from January 31, 2018, to February 20, 2020. Twenty-two eyes of 22 patients with PXE and 40 eyes of 40 healthy individuals were included. Data analysis was completed March 15, 2020.EXPOSURES Mesopic and dark-adapted 2-color fundus-controlled perimetry (microperimetry) and multimodal retinal imaging including spectral-domain optical coherence tomography (SD-OCT) and OCT angiography were performed. Perimetry thresholds were analyzed using mixed models, and structure-function correlation with SD-OCT data was performed using machine learning. MAIN OUTCOMES AND MEASURESObserved dark-adapted cyan sensitivity loss as measure of rod photoreceptor dysfunction, as well as mean absolute error between predicted and observed retinal sensitivity to assess the accuracy of structure-function correlation. RESULTSOf the 22 patients with PXE included in this study, 15 were women (68%); median age was 56.5 years (interquartile range, 50.4-61.2). These patients exhibited mesopic (estimate, 5.13 dB; 95% CI, 2.89-7.38 dB), dark-adapted cyan (estimate, 9.08 dB; 95% CI, 6.34-11.82 dB), and dark-adapted red (estimate, 7.05 dB; 95% CI, 4.83-9.27 dB) sensitivity losses. This sensitivity loss was also evident in 9 eyes with nonneovascular PXE (mesopic: estimate, 3.21 dB; 95% CI, 1.28-5.14 dB; dark-adapted cyan: 5.93 dB; 95% CI, 3.59-8.27 dB; and dark-adapted red testing: 4.84 dB; 95% CI, 2.88-6.80 dB), showing a distinct centrifugal pattern of sensitivity loss with preserved function toward the periphery. Retinal function could be predicted from microstructure with high accuracy (mean absolute errors, of 4.91 dB for mesopic, 5.44 dB for dark-adapted cyan, and 4.99 dB for dark-adapted red). The machine learning-based analysis highlighted an association of a thinned inner retina and putative separation of the pigment-epithelium-photoreceptor complex with sensitivity loss. CONCLUSIONS AND RELEVANCEIn this study, among 22 patients with PXE, those with and without choroidal neovascularization exhibited reductions of retinal sensitivity being most pronounced in dark-adapted cyan testing. This finding suggests that pathologic characteristics of this Bruch membrane disease may be dominated by rod photoreceptor degeneration and/or dysfunction. A putative pigment-epithelium-photoreceptor separation may further impair rod function, while inner retinal abnormalities appear to be correlated with overall dysfunction.

Dark adaptation (DA) refers to the slow recovery of visual sensitivity in darkness following exposure to intense or prolonged illumination, which bleaches a significant amount of the rhodopsin. This natural process also offers an opportunity to understand cellular function in the outer retina and evaluate for presence of disease. How our eyes adapt to darkness can be a key indicator of retinal health, which can be altered in the presence of certain diseases, such as age-related macular degeneration (AMD). A specific focus on clinical aspects of DA measurement and its significance to furthering our understanding of AMD has revealed essential findings underlying the pathobiology of the disease. The process of dark adaptation involves phototransduction taking place mainly between the photoreceptor outer segments and the retinal pigment epithelial (RPE) layer. DA occurs over a large range of luminance and is modulated by both cone and rod photoreceptors. In the photopic ranges, rods are saturated and cone cells adapt to the high luminance levels. However, under scotopic ranges, cones are unable to respond to the dim luminance and rods modulate the responses to lower levels of light as they can respond to even a single photon. Since the cone visual cycle is also based on the Muller cells, measuring the impairment in rod-based dark adaptation is thought to be particularly relevant to diseases such as AMD, which involves both photoreceptors and RPE. Dark adaptation parameters are metrics derived from curve-fitting dark adaptation sensitivities over time and can represent specific cellular function. Parameters such as the cone-rod break (CRB) and rod intercept time (RIT) are particularly sensitive to changes in the outer retina. There is some structural and functional continuum between normal aging and the AMD pathology. Many studies have shown an increase of the rod intercept time (RIT), i.e., delays in rod-mediated DA in AMD patients with increasing disease severity determined by increased drusen grade, pigment changes and the presence of subretinal drusenoid deposits (SDD) and association with certain morphological features in the peripheral retina. Specifications of spatial testing location, repeatability of the testing, ease and availability of the testing device in clinical settings, and test duration in elderly population are also important. We provide a detailed overview in light of all these factors.

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