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Purpose: To investigate the temporal sequence of changes in the photoreceptor cell mosaic in patients with Stargardt disease type 1, using adaptive optics scanning laser ophthalmoscopy., Methods: Two brothers with genetically confirmed Stargardt disease type 1 underwent comprehensive eye exams, spectral-domain optical coherence tomography, fundus autofluorescence, and adaptive optics scanning laser ophthalmoscopy imaging 3 times over the course of 28 months. Confocal images of the cones and rods were obtained from the central fovea to 10° inferiorly. Photoreceptors were counted in sampling windows at 100- µ m intervals of 200 µ m × 200 µ m for cones and 50 µ m × 50 µ m for rods, using custom cell marking software with manual correction. Photoreceptor density and spacing were measured and compared across imaging sessions using one-way analysis of variance., Results: Adaptive optics scanning laser ophthalmoscopy revealed the younger brother had a 30% decline in foveal cone density after 8 months, followed by complete loss of foveal cones at 28 months; the older brother had no detectable foveal cones at baseline. In the peripheral macula, cone and rod spacings were greater than normal in both patients. The ratio of the cone spacing to rod spacing was greater than normal across all eccentricities, with a greater divergence closer to the foveal center., Conclusion: Cone cell loss may be an early pathogenetic step in Stargardt disease. Adaptive optics scanning laser ophthalmoscopy provides the capability to track individual photoreceptor changes longitudinally in Stargardt disease.

Purpose: To investigate cone density in the asymptomatic fellow eye of patients with unilateral central serous chorioretinopathy (CSCR)., Methods: Seventeen asymptomatic fellow eyes of patients with unilateral CSCR and 17 eyes of aged-matched and gender-matched healthy controls underwent adaptive optics ophthalmoscopy. Cone density and spacing were assessed at the fovea. Clinical and multimodal imaging findings were also recorded., Results: In the CSCR group, the patient mean age was 48.9 ± 9.8 years. The mean (±SD) subfoveal choroidal thickness was 417.8 ± 125.2 µm. The foveal external limiting membrane and ellipsoid zone were intact in all patients. Adaptive optics fundus imaging showed a significant decrease in cone density at 2° of eccentricity nasal and temporal to the fovea in asymptomatic fellow eyes of patients with unilateral CSCR compared with controls (P = 0.001 and P = 0.027, respectively). No statistically significant difference in cone density was found at 4° of eccentricity nasal and temporal to the fovea between both groups., Conclusion: Asymptomatic fellow eyes of patients with unilateral CSCR showed a reduced density of foveal cones in the absence of a decreased visual acuity and photoreceptor line disruption on optical coherence tomography. These results suggest that the photoreceptors could be damaged independently of the occurrence of a serous retinal detachment., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Significance: Cone dystrophies and cone-rod dystrophies are a group of rare inherited pathologies characterized by degeneration of cone photoreceptors and subsequent rod involvement. The identification of causative genes is essential for diagnosis, and advanced imaging is acquiring great value in the characterization of the different phenotypic expressions., Purpose: We describe genotype-phenotype associations of an autosomal recessive ABCA4-associated cone dystrophy using multimodal imaging., Case Report: A 34-year-old woman presented with progressive visual acuity decay. Visual acuity was 20/32 for her right eye and 20/25 for her left eye. A central scotoma was detected on a 10-2 Humphrey visual field in both eyes. Funduscopy revealed perifoveal retinal pigment epithelial changes, and fundus autofluorescence using blue excitation light showed decreased autofluorescence in the central fovea of both eyes with surrounding annular ring of increased autofluorescence in the perifoveal zone; green excitation light fundus autofluorescence was more accurate in the characterization of the size, perimeter, and circularity of central hypofluorescent lesions. Optical coherence tomography revealed an incomplete focal cavitation in both foveas, and optical coherence tomography angiography images showed a reduction in the superficial and deep capillary plexus density, an increased foveal avascular area, and subtle voids in choriocapillaris blood flow. Electroretinography was consistent with cone dystrophy, and molecular testing revealed the alteration of the ABCA4 gene., Conclusions: The identification of an incomplete focal cavitation could alert the clinician to consider early ABCA4 central cone dystrophy. The patient in this case also exhibited reduced vessel density in the foveal area. Both of these characteristics could be important features related to the underlying genetic mutation., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2021 American Academy of Optometry.)

Purpose: To examine hypotony-associated foveal lesions (FovLs) using optical coherence tomography, and to assess the risk factors of visual deterioration after glaucoma filtering surgery., Methods: Parameters that may be associated with postsurgical deterioration of visual acuity were retrospectively studied in 44 eyes of 44 patients who experienced postsurgical intraocular hypotension ≤6 mmHg between 2015 and 2019., Results: Six eyes (14%) had FovLs, such as detachment of photoreceptors (5 eyes, 11%) and acquired vitelliform lesions (1 eye, 2%) at 3 months after trabeculectomy. Logistic regression analysis revealed that hypotony maculopathy (P = 0.0141 at 3 months) and FovLs (P = 0.0486 and 0.0296 at 3 and 12 months, respectively) were significant risk factors for Visual acuity loss after trabeculectomy. The FovLs were located just behind the Müller cell cone. Visual acuity at 3 and 12 months after surgery in patients with FovLs was significantly lower than in those without FovLs (P = 0.0013 and P = 0.006, respectively). Epiretinal membrane was more common in eyes with FovLs (5 of 6 eyes, 83%) than in eyes without FovLs (7 of 38 eyes, 18%; P = 0.0037)., Conclusion: Müller cell cone-associated FovLs lead to long-lasting visual acuity loss after filtering surgery., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Purpose: To clarify the histologic basis of bacillary layer detachment (BALAD) through a review of the current literature and an analysis of retinal imaging., Methods: The literature for previous reports of BALAD were reviewed. An analysis of retinal images was performed to support anatomical conclusions., Results: A total of 164 unique patients with BALAD on optical coherence tomography (OCT) were identified from the published literature. Twenty-two underlying etiologies, all associated with subretinal exudation, were identified. Forty-one different OCT terminologies were found. The defining OCT feature of BALAD was a split at the level of the photoreceptor inner segment myoid creating a distinctive intraretinal cavity. Resolution of BALAD was followed by a rapid restoration of the ellipsoid zone. Histology of age-related macular degeneration eyes suggests that individual photoreceptors can shed inner segments. Furthermore, detachment of the entire layer of inner segments is a common postmortem artifact. It is proposed that BALAD occurs when outwardly directed forces promoting attachment of photoreceptor outer segments to the retinal pigment epithelium exceed the tensile strength of the photoreceptor inner segment myoid., Conclusion: This review serves to strengthen the OCT nomenclature "bacillary layer detachment," based on specific reflectance information obtained by OCT and previously published histologic observations.

Purpose: Macular edema is a common retinal disease which may leave important anatomical and functional sequelaes. Directional fundus imaging consists of comparing on- and off-axis images to reveal angle-dependent reflectance properties of fundus structures, which may be related to misaligned photoreceptors. Here, we analyzed directional optical coherence tomography (OCT) and flood-illumination adaptive optics ophthalmoscopy images to detect evidence of misaligned photoreceptors following macular edema., Methods: Transversal, observational study. Nine patients having recovered a normal macular profile after macular edema due to retinal vein occlusion were included. For each patient, a reference OCT scan (i.e., with the incident beam normal to the fovea) was acquired, and off-axis scans were then acquired by laterally shifting the entry pupil. In addition, in four of these eyes, directional adaptive optics ophthalmoscopy documented the directional variations of cone metrics., Results: Included patients comprised two women and seven men (age range, 19-76 years). Reference OCT scans showed patchy attenuation of the cone outer segment tips and to a lesser extent of the inner segment/outer segment lines in all, but two eyes; these. Increased intensity of the cone outer segment tips and inner segment/outer segment lines could be observed on off-axis scans. Accordingly, fusion images showed 66% average reduction of the length of cone outer segment tips attenuation. In two cases, although reference scans showed continuity of outer bands, focal attenuation was evidenced in off-axis images. Directional adaptive optics ophthalmoscopy imaging showed a strong directional variability of cone counts in these areas, ranging from near absence to roughly two-third of reference values. In each case, directional variations of cone counts paralleled those of the reflectance of outer bands., Conclusion: After macular edema, focal attenuations of the inner segment/outer segment and of the cone outer segment tips lines may be present on OCT. These areas may show a strong directional variability by both OCT and adaptive optics ophthalmoscopy, suggesting that misaligned photoreceptor outer segments contribute to such features. The evaluation of outer retinal damage following macular edema should therefore take into account the optical Stiles-Crawford effect to disambiguate missing from misaligned cones.

Purpose: To assess the status of the cone photoreceptors using adaptive optics flood illumination ophthalmoscopy in patients with birdshot chorioretinopathy and to study their relationship with optical coherence tomography (OCT) angiography., Methods: Seventeen patients with birdshot chorioretinopathy were studied using standard automated perimetry, color vision testing, fluorescein angiography, indocyanine green angiography, spectral domain OCT, enhanced depth imaging OCT, and adaptive optics flood illumination ophthalmoscopy (rtx1, Imagine Eyes, Orsay, France) in a 90 × 90-μm area at 1.5° temporal of the fovea and OCT angiography (Spectralis OCT2, Heidelberg Engineering, Heidelberg, Germany). For adaptive optics flood illumination ophthalmoscopy, spectral domain OCT, and OCT angiography, a control group of 12 healthy patients (12 eyes) matched for age, sex, and refractive error was included., Results: After excluding low-quality adaptive optics flood illumination ophthalmoscopy images, 12 eyes (12 patients, 7 women, mean age 53.5 ± 10.8 years) were analyzed. Best-corrected visual acuity was 0.01 ± 0.03 LogMAR (20/25 Snellen equivalent), and foveal threshold at standard automated perimetry was 35.2 ± 3.0. Cone density at 1.5° of the fovea in the birdshot chorioretinopathy group (11,435.25 ± 4,342.9 cells/mm) was significantly smaller than in the control group (24,594.04 ± 4,764.3 cells/mm, P < 0.001). In the same area, birdshot chorioretinopathy eyes showed disruption of the ellipsoid/interdigitation zone and vascular abnormalities, such as capillary loops (58.3%), increased superficial intercapillary spaces (75%), increased deep intercapillary spaces (58.3%), capillary dilations (58.3%), telangiectatic vessels (66.6%), and absence of choriocapillary flow (58%). Cone density at 1.5° was associated with duration of the disease (Spearman's rho -0.8, P = 0.01), although it was not associated with OCT angiography abnormalities in the same area., Conclusion: Birdshot chorioretinopathy can result in a reduction in cone density and development of macular vascular abnormalities even in the presence of preserved visual function.

This study analyzed cone density, cone mosaic, and fundus autofluorescence (FAF) images in patients with focal laser-treated central serous chorioretinopathy (CSC).Observational case series.Forty-two eyes of 21 patients with unilateral treated CSC and bilateral best-corrected visual acuity of 1.0 (decimal fraction) were included. FAF and cone mosaic images were obtained in all patients with an adaptive optics fundus camera. Densities were recorded at 20 points throughout the macula, and choroidal thicknesses were measured.Mean choroidal thicknesses were 419.95 ± 110.33 μm in normal eyes, 459.09 ± 90.07 μm in eyes with active CSC, and 438.61 ± 107.57 μm in treated eyes. The highest density of cones in healthy eyes was 38146 cones/mm, with a 5.66-μm intercellular space (IS), at 700 μm temporal to the center. In eyes with treated CSC, the highest density was 32749 cones/mm, with a 6.13-μm IS, at 500 μm nasal to the center. In all quadrants, median values of maximum cone density were significantly higher in healthy eyes (P = .02, P = .003, P = .0001, and P = .001). Three types of lesions were identified on FAF and were correlated with those on cone mosaic images. Strong correlations were detected between the presence of hypoautofluorescent lesions on the first FAF image and a greater difference between maximum values of photoreceptor density (r = 0.46, P = .03), as well as between the presence of hypoautofluorescent lesions and the duration of pathology (r = 0.68, P < .001).The presence of hypoautofluorescent lesions and the duration of pathology were negative prognostic factors in CSC. Laser treatment could prevent photoreceptor loss.

Purpose: To quantify changes in photoreceptor density using adaptive optics fundus camera in patients after retinal detachment (RD) and to correlate them with macular involvement and best-corrected visual acuity., Methods: At 1 and 3 months (M1 and M3) after vitrectomy, 194 patients underwent adaptive optics imagery in both eyes, at 5 locations, that we matched between time points using anatomical landmarks. Twenty-two patients (10 fovea-OFF [OFF] and 12 fovea-ON [ON]) had matched and analyzable adaptive optics images. We used analysis of variance for repeated measures., Results: Best-corrected visual acuity (logarithm of the minimum angle of resolution and Snellen equivalent [SE]) was significantly different between OFF and ON RDs at baseline: 2.0 (2.3-0.95) (SE: 20/2000) versus 0 (0.1-0) (SE: 20/20); at M1: 0.35 (0.5-0.1) (SE: 20/40) versus 0.05 (0-0.1) (SE: 20/25); and at M3: 0.25 (0.3-0.1) (SE: 20/32) versus 0 (0-0) (SE: 20/20). We observed that cone density was stable in fellow eyes between M1 and M3 (P = 0.67); decreased in treated eyes than in fellow eyes (P < 0.05); and increased postoperatively in the ON group (P = 0.02) but not in the OFF group (P = 0.97). Visual acuity and RD type were independently correlated with cone density (P = 0.004, P = 0.000)., Conclusion: Postoperative cone density was reduced in OFF RD, but also in the ON group, although the drop recovered during the 3-month follow-up. Cone density was significantly correlated with both visual acuity and type of RD at both time points.

Purpose: To assess the morphological changes of cone photoreceptors in eyes with autosomal recessive bestrophinopathy., Methods: Both eyes of five patients with autosomal recessive bestrophinopathyunderwent spectral domain optical coherence tomography and adaptive optics fundus imaging. The cone photoreceptor densities were measured at intervals of 100 μm between 500 μm nasal and temporal eccentricities from the foveal center., Results: The median age of the patients was 30 years (range, 23-45 years), and the best-corrected visual acuity ranged from 20/20 to 20/80. Adaptive optics fundus images showed reduced cone photoreceptor densities corresponding to the damages of the photoreceptor layer in the spectral domain optical coherence tomography images in four patients with relatively good best-corrected visual acuity. The cone photoreceptor densities at the center of the fovea were less than one-third of the normal cone densities (range 11,600-30,400 cells/mm). Cone photoreceptor mosaics were visible over the lesions with serous retinal detachment and retinal edema, although they were partially hyporeflective., Conclusion: There is a significant cone photoreceptor loss in the macular region of patients with autosomal recessive bestrophinopathy, although they had relatively good visual acuity. Monitoring cone photoreceptors by adaptive optics fundus imaging should provide accurate assessments of the disease status and indications for future therapeutic interventions.

Purpose: To examine the features of the tapetal-like reflex (TLR) in female carriers of RPGR-associated retinopathy by means of adaptive optics scanning light ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography., Methods: Nine molecularly confirmed RPGR carriers and three healthy controls underwent ocular examination and the following retinal imaging modalities: color photography, near-infrared reflectance, fundus autofluorescence, spectral domain optical coherence tomography, and AOSLO. After identifying TLR areas across all imaging modalities, normalized local contrast of outer retinal bands on spectral domain optical coherence tomography was calculated and AOSLO-acquired photoreceptor mosaic analysis was performed., Results: Seven carriers had TLR areas, which colocalized with increased rod photoreceptor reflectivity on confocal AOSLO and reduced cone photoreceptor densities. Parafoveal TLR areas also exhibited reduced local contrast (i.e., increased reflectivity) of the outer retinal bands on spectral domain optical coherence tomography (inner segment ellipsoid zone and outer segment interdigitation zone). Healthy controls did not show TLR., Conclusion: The cellular resolution provided by AOSLO affords the characterization of the photoreceptor mosaic in RPGR carriers with a TLR. Features revealed include reduced cone density, increased cone inner segment diameter, and increased rod outer segment reflectivity.

Significance: The Farnsworth D15 test can be subverted by patients even with severe red-green color deficiency., Purpose: To describe a case showing that perfect performance on the Farnsworth D15 is possible after practicing the test., Case Report: A 23-year-old man presented for a comprehensive color vision evaluation. He had only minor complaints with regard to color vision and otherwise normal vision and ocular health. Based on anomaloscope findings, he was diagnosed with protanopia, a form of dichromacy in which the patient does not have any functional L cones, only S and M cones. The patient practiced the Farnsworth D15 test and returned for a follow-up visit in which he performed the test perfectly four times (i.e., twice in the regular order and twice using cap 15 as the pilot cap). In addition, the patient returned a year later and again performed the test perfectly, indicating long-term learning., Conclusions: All studies to date have shown that patients with dichromacy fail the Farnsworth D15 test. This case report shows that it is indeed possible for highly motivated patients to subvert the test through practice, and knowledge of this possibility is very important, especially in occupational testing.

Purpose: Widespread adoption of optical coherence tomography has revolutionized the diagnosis and management of retinal disease. If the cellular and subcellular sources of reflectivity in optical coherence tomography can be identified, the value of this technology will be advanced even further toward precision medicine, mechanistic thinking, and molecular discovery. Four hyperreflective outer retinal bands are created by the exquisite arrangement of photoreceptors, Müller cells, retinal pigment epithelium, and Bruch membrane. Because of massed effects of these axially compartmentalized and transversely aligned cells, reflectivity can be localized to the subcellular level. This review focuses on the second of the four bands, called ellipsoid zone in a consensus clinical lexicon, with the central thesis that mitochondria in photoreceptor inner segments are a major independent reflectivity source in this band, because of Mie scattering and waveguiding., Methods: We review the evolution of Band 2 nomenclature in published literature and discuss the origins of imaging signals from photoreceptor mitochondria that could make these organelles visible in vivo., Results: Our recent data pertain to outer retinal tubulation, a unique neurodegenerative and gliotic structure with a highly reflective border, prominent in late age-related macular degeneration. High-resolution histology and multimodal imaging of outer retinal tubulation together provide evidence that inner segment mitochondria undergoing fission and translocation toward the nucleus provide the reflectivity signal., Conclusion: Our data support adoption of the ellipsoid zone nomenclature. Identifying subcellular signal sources will newly inform clinical.

Purpose: To characterize lesions of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) by multimodal imaging including adaptive optics scanning laser ophthalmoscopy (AOSLO)., Methods: We included patients with APMPPE at different stages of evolution of the placoid lesions. Color fundus photography, spectral domain optical coherence tomography, infrared reflectance, fundus autofluorescence, and AOSLO images were obtained and registered to correlate microstructural changes., Results: Eight eyes of four patients (two women) were included and analyzed by multimodal imaging. Photoreceptor reflectivity within APMPPE lesions was more heterogeneous than in adjacent healthy areas. Hyperpigmentation on color fundus photography appeared hyperreflective on infrared reflectance and on AOSLO. Irregularity of the interdigitation zone and the photoreceptor inner and outer segment junctions (IS/OS) on spectral domain optical coherence tomography was associated with photoreceptor hyporeflectivity on AOSLO. Interruption of the interdigitation zone or IS/OS was associated with loss of photoreceptor reflectivity on AOSLO., Conclusion: Irregularities in the reflectivity of the photoreceptor mosaic are visible on AOSLO even in inactive APMPPE lesions, where the photoreceptor bands on spectral domain optical coherence tomography have recovered. Adaptive optics scanning laser ophthalmoscopy combined with multimodal imaging has the potential to enhance our understanding of photoreceptor involvement in APMPPE.

Purpose: Congenital achromatopsia is an autosomal recessive disease causing substantial reduction or complete absence of cone function. Although believed to be a relatively stationary disorder, questions remain regarding the stability of cone structure over time. In this study, the authors sought to assess the repeatability of and examine longitudinal changes in measurements of central cone structure in patients with achromatopsia., Methods: Forty-one subjects with CNGB3-associated achromatopsia were imaged over a period of between 6 and 26 months using optical coherence tomography and adaptive optics scanning light ophthalmoscopy. Outer nuclear layer (ONL) thickness, ellipsoid zone (EZ) disruption, and peak foveal cone density were assessed., Results: ONL thickness increased slightly compared with baseline (0.184 μm/month, P = 0.02). The EZ grade remained unchanged for 34/41 subjects. Peak foveal cone density did not significantly change over time (mean change 1% per 6 months, P = 0.126)., Conclusion: Foveal cone structure showed little or no change in this group of subjects with CNGB3-associated achromatopsia. Over the time scales investigated (6-26 months), achromatopsia seems to be a structurally stable condition, although longer-term follow-up is needed. These data will be useful in assessing foveal cone structure after therapeutic intervention.

Purpose: To investigate the microscopic structure of outer retinal tubulation (ORT) and optical properties of cone photoreceptors in vivo, we studied ORT appearance by multimodal imaging, including spectral domain optical coherence tomography (SD-OCT) and adaptive optics scanning laser ophthalmoscopy., Methods: Four eyes of four subjects with advanced age-related macular degeneration underwent color fundus photography, infrared reflectance imaging, SD-OCT, and adaptive optics scanning laser ophthalmoscopy with a high-resolution research instrument. Outer retinal tubulation was identified in closely spaced (11 μm) SD-OCT volume scans., Results: Outer retinal tubulation in cross-sectional and en face SD-OCT was a hyporeflective area representing a lumen surrounded by a hyperreflective border consisting of cone photoreceptor mitochondria and external limiting membrane, per previous histology. In contrast, ORT by adaptive optics scanning laser ophthalmoscopy was a hyporeflective structure of the same shape as in en face SD-OCT but lacking visualizable cone photoreceptors., Conclusion: Lack of ORT cone reflectivity by adaptive optics scanning laser ophthalmoscopy indicates that cones have lost their normal directionality and waveguiding property due to loss of outer segments and subsequent retinal remodeling. Reflective ORT cones by SD-OCT, in contrast, may depend partly on mitochondria as light scatterers within inner segments of these degenerating cells, a phenomenon enhanced by coherent imaging. Multimodal imaging of ORT provides insight into cone degeneration and reflectivity sources in optical coherence tomography.

Purpose: To characterize outer retina structure in best vitelliform macular dystrophy (BVMD) and to determine the effect of macular lesions on overlying and adjacent photoreceptors., Methods: Five individuals with BVMD were followed prospectively with spectral domain optical coherence tomography and confocal and nonconfocal split-detector adaptive optics scanning light ophthalmoscopy (AOSLO). The AOSLO cone photoreceptor mosaic images were obtained within and around retinal lesions. Cone density was measured inside and outside lesions. In 2 subjects, densities were compared with published measurements acquired ∼2.5 years before. One subject was imaged 3 times over a 5-month period., Results: The AOSLO imaging demonstrated that photoreceptor morphology within BVMD retinal lesions was highly variable depending on the disease stage, with photoreceptor structure present even in advanced disease. The AOSLO imaging was repeatable even in severe disease over short-time and long-time intervals. Photoreceptor density was normal in retinal areas immediately adjacent to lesions and stable over ∼2.5 years. Mobile disk-like structures possibly representing subretinal macrophages were also observed., Conclusion: Combined confocal and nonconfocal split-detector AOSLO imaging reveals substantial variability within clinical lesions in all stages of BVMD. Longitudinal cellular photoreceptor imaging could prove a powerful tool for understanding disease progression and monitoring emerging therapeutic treatment response in inherited degenerations such as BVMD.

Purpose: Photophobia is a debilitating clinical condition that disrupts the ability to use vision for everyday tasks in bright lighting conditions. The goal of the study is to develop a methodology to study the neural basis of photophobia and the contribution of the melanopic pathway to its etiology with differential chromatic responses by means of standard electroencephalographic recording equipment., Methods: We introduce and validate the approach of recording wavelength-specific electroretinographic (ERG) responses from the face electrodes of the high-density whole-head electroencephalography recording system under light-adapted conditions., Results: ERGs recorded in this way to whole-field chromatic stimuli exhibit striking differences between the photophobic and non-photophobic groups. The control responses were consistent with photopic intensity in peak time, and in the ordering of peak times as a function of wavelength condition, indicating a predominantly cone source of the signals. The photophobic responses, on the other hand, were substantially slowed relative to controls, with the peak times conforming to a different order as a function of wavelength condition than controls, implying that the cone response has been suppressed and that the responses derived from a different photoreceptor system consistent with mediation by melanopic retinal ganglion cells., Conclusions: The results will be important for determining the neural pathways involved in photophobia and potential approaches to its treatment on the basis of this etiology.

Purpose: To assess macular microstructure in eyes with tilted disk syndrome (TDS) and determine the relationship between TDS foveal morphology and visual function., Methods: Twenty-six TDS eyes from 19 children (aged 5∼15 years) with a spherical equivalent refraction (SER) of -3.1 ± 1.3 diopter (D) and 28 control eyes from 14 children (aged 7∼12 years) with a SER of -3.0 ± 0.7 D were recruited. Horizontal and vertical optical coherence tomography scans through the fovea produced images that were segmented into eight intraretinal layers. Thicknesses of the total retina and each layer were measured at the foveal center and 12 other macular locations: 500 μm, 1,000 μm, and 1,500 μm along the horizontal and vertical meridians. The relationships between TDS best correct visual acuity (BCVA) and the presence of photoreceptor inner/outer segment (IS/OS) junction line, IS/OS foveal bulge, and cone outer segment tip (COST) line were evaluated., Results: The thickness of TDS central fovea, 218.94 ± 22.20 μm, was not significantly different from controls. The total retinal thickness in TDS eyes was thinner than controls at all peripheral locations (P < 0.05) except at 500 μm and 1,000 μm superiorly, and 1,500 μm temporally. Tilted disk syndrome intraretinal layer thicknesses in the nasal and inferior regions varied significantly from controls (P < 0.05). Only 80.7% and 23.1% of TDS eyes had a normal foveal bulge and continuous COST line, respectively, compared with 100% and 96.4% of controls. The BCVA of TDS eyes was similar whether or not the foveal bulge or COST line was abnormal., Conclusion: Differences in intraretinal layer thickness may be correlated with defective vision.

Purpose: To analyse whether the size of internal limiting membrane peeling influences the outcome of macular hole surgery., Methods: Prospective, comparative, interventional study. Fifty eyes were included. Twenty-five eyes had smaller (3-mm) peel (Group 1), whereas the other 25 had larger (5-mm) peel (Group 2). Outcome measures were macular hole closure rate, improvement in best corrected visual acuity, retinal nerve fiber layer, and ganglion cell layer thickness (0.5 mm, 1.5 mm, and 2.5 mm temporal and medial to the fovea), external limiting membrane, inner segment outer segment layer, and cone outer segment tip restoration., Results: Both the groups were matched for demographic parameters, spectral-domain optical coherence tomography-based macular hole staging and dimensions. Hole closure rates were similar, 80% and 65% in Group 1 and 2, respectively (P = 0.20). No difference was observed in anatomical success rate, irrespective of size, stage, or duration of hole. Visual improvement was better in Group 1 (4 lines vs. 2-line Early Treatment Diabetic Retinopathy Study equivalent; P = 0.04); the retinal nerve fiber layer was thinner at all locations in Group 2, with the difference being significant, 2.5 mm temporal to the fovea (P < 0.05), whereas the ganglion cell layer was thicker in the 3-mm group, significantly so at the location, 1.5 mm temporal to the fovea (P = 0.01). Outer layer restoration rates were also similar in both the groups., Conclusion: Macular hole closure rate was similar in both the groups; however, smaller (3-mm) peel group demonstrated better functional improvement and nerve fiber layer preservation.

Purpose: To illustrate altered fundus autofluorescence in rubella retinopathy and to investigate their relationships with photoreceptor structure and function using multimodal imaging., Methods: The authors report four cases of rubella retinopathy aged 8, 33, 42, and 50 years. All patients had dilated clinical fundus examination; wide-field color photography; blue, green, and near-infrared autofluorescence imaging and spectral domain optical coherence tomography. Two patients also underwent microperimetry and adaptive optics imaging. En face optical coherence tomography, cone mosaic, and microperimetry were coregistered with autofluorescence images. The authors explored the structure-function correlation., Results: All four patients had a "salt-and-pepper" appearance on dilated fundus examination and wide-field color photography. There were variable-sized patches of hypoautofluorescence on both blue and near-infrared excitation in all four patients. Wave-guiding cones were visible and retinal sensitivity was intact over these regions. There was no correlation between hypoautofluorescence and regions of attenuated ellipsoid and interdigitation zones. Hyperautofluorescent lesions were also noted and some of these were pseudo-vitelliform lesions., Conclusion: Patchy hypoautofluorescence on near-infrared excitation can be a feature of rubella retinopathy. This may be due to abnormal melanin production or loss of melanin within retinal pigment epithelium cells harboring persistent rubella virus infection. Preservation of the ellipsoid zone, wave-guiding cones, and retinal sensitivity within hypoautofluorescent lesions suggest that these retinal pigment epithelium changes have only mild impact on photoreceptor cell function.

Purpose: To report the characteristic changes of fundus autofluorescence in the nasal retina of patients with retinitis pigmentosa., Methods: We investigated 113 eyes of 113 patients with retinitis pigmentosa. We obtained wide-field fundus autofluorescence images and evaluated the status of the retina nasal to the optic disk. The patients were divided into the following three groups: those without nasal sparing (advanced), those with nasal sparing, and those with larger intact areas in addition to the nasal retina (early). Visual acuity, visual field area, age, and the duration of the symptom were compared among the groups., Results: Twenty eyes (17.7%), 51 (45.1%), and 42 (37.1%) were classified as early, nasal sparing, and advanced, respectively. The nasal retina was essentially preserved in the early group. The clinical characteristics' analysis suggested that the disease progression appears from that represented by early groups, then nasal sparing groups, and finally advanced groups. The authors found that the nasal sparing pattern bears a close resemblance to the previously reported cone photoreceptor distribution., Conclusion: Wide-field fundus autofluorescence imaging detected nasal sparing in retinitis pigmentosa. The characteristic fundus autofluorescence pattern should reflect cone photoreceptor distribution in the human retina. This finding may be an example of the clinical appearance of asymmetric photoreceptor distribution.

Purpose: To determine whether cone photoreceptors are impaired early in macular telangiectasia type 2 (MacTel 2) progression., Methods: Eight patients with MacTel 2 lacking intraretinal cavitation underwent multimodal retinal imaging including adaptive optics. Cone packing metrics were determined in 5 sampling windows at different eccentricities from the fovea. Results were compared with a previously established normative database., Results: In MacTel 2 eyes, cone density was significantly lower than normal at all eccentricities (P < 0.0001). Mean cone spacing and mean percentage of hexagonally organized cone photoreceptors were respectively significantly larger and lower than normal at all eccentricities (P = 0.0488 and P < 0.0001). In MacTel 2 patients, adaptive optics showed an irregular patchy disturbance of the cone mosaic corresponding to some fragmentation of the interdigitation zone on optical coherence tomography. The ellipsoid zone remained intact in the studied area., Conclusion: Adaptive optics showed that the macular cone density was lower than normal even outside the telangiectasia in MacTel 2 lacking intraretinal cavitation, although the ellipsoid zone remained intact on optical coherence tomography. These findings do not indicate that the cone density loss is causative of the disease as it might be secondary to Müller cell or rod loss in this area. However, cone density assessment could become a useful parameter to monitor disease progression.

Purpose: Utilize high-resolution imaging to examine retinal anatomy in patients with known genetic relative risk (RR) for developing age-related macular degeneration (AMD)., Methods: Forty asymptomatic subjects were recruited (9 men, 31 women; age range, 51 to 69 years; mean age, 61.4 years). Comprehensive eye examination, fundus photography, and high-resolution retinal imaging using spectral domain optical coherence tomography and adaptive optics were performed on each patient. Genetic RR scores were developed using an age-independent algorithm. Adaptive optics scanning light ophthalmoscope images were acquired in the macula extending to 10 degrees temporal and superior from fixation and were used to calculate cone density in up to 35 locations for each subject., Results: Relative risk was not significantly predictive of fundus grade (p = 0.98). Only patients with a high RR displayed drusen on Cirrus or Bioptigen OCT. Compared to an eye with a grade of 0, an eye with a fundus grade equal to or greater than 1 had a 12% decrease in density (p < 0.0001) and a 5% increase in spacing (p = 0.0014). No association between genetic RR and either cone density (p = 0.435) or spacing (p = 0.538) was found. Three distinct adaptive optics scanning light ophthalmoscope phenotypical variations of photoreceptor appearance were noted in patients with grade 1 to 3 fundi. These included variable reflectivity of photoreceptors, decreased waveguiding, and altered photoreceptor mosaic overlying drusen., Conclusions: Our data demonstrate the potential of multimodal assessment in the understanding of early anatomical changes associated with AMD. Adaptive optics scanning light ophthalmoscope imaging reveals a decrease in photoreceptor density and increased spacing in patients with grade 1 to 3 fundi, as well as a spectrum of photoreceptor changes, ranging from variability in reflectivity to decreased density. Future longitudinal studies are needed in genetically characterized subjects to assess the significance of these findings with respect to the development and progression of AMD.

Purpose: To describe multimodal imaging and electrophysiologic characteristics of an unusual subset of patients with genetically confirmed autosomal recessive Stargardt disease (STGD1) who exhibited a central form of cone dysfunction resembling occult macular dystrophy that preceded the development of lipofuscin flecks, atrophy of retinal pigment epithelium (RPE), or full-field electroretinography abnormalities., Methods: Retrospective, observational descriptive case series., Results: Five patients with compound heterozygous ABCA4 mutations presented with bilateral visual acuity reduction, normal-appearing fundi, and blocked choroidal fluorescence on fluorescein angiography. One sibling each of two probands with identical genotypes was also included for analysis. Full-field electroretinography testing was normal in all patients, but multifocal electroretinography demonstrated centripetally depressed amplitudes exceeding areas of fundus autofluorescence, infrared imaging, and spectral domain optical coherence tomography abnormalities. Spectral domain optical coherence tomography initially revealed disruption of the inner segment ellipsoid band accompanying an ovoid hypofluorescent foveolar lesion. Progression to later stages was accompanied by the loss of the foveal photoreceptor outer segments, creating foveal cavitation with preservation of the RPE. Fundus autofluorescence and infrared imaging demonstrated corresponding bull's eye lesions. Over time, the foveal potential space on spectral domain optical coherence tomography collapsed, and three patients developed RPE atrophy and visible lipofuscin flecks. The flecks were detectable by fundus autofluorescence and infrared imaging earlier than by biomicroscopy. From these findings, a staging system for this subset of Stargardt disease presenting with central cone dysfunction was developed and presented herein., Conclusion: Autosomal recessive Stargardt disease may present as a central cone dysfunction syndrome before the development of lipofuscin flecks, atrophy of RPE, or full-field electroretinography abnormalities. If emerging therapies for Stargardt disease succeed, early recognition and treatment of patients with preserved foveal photoreceptor and RPE cell bodies may yield a more favorable visual prognosis.

Purpose: High myopia (HM) is one of the leading causes of irreversible blindness because of its associated complications. Early-onset HM (eoHM) that presents before primary school age may be genetically determined, whereas late-onset HM (loHM) is affected by genetic and environmental factors. Identification of signs that differentiate eoHM from loHM may provide valuable clues toward understanding the molecular basis of HM., Methods: In this study, 42 subjects with HM were recruited, including 32 eoHM (onset age, ≤5 years) and 10 loHM (onset age, 12.4 ± 2.5 years). Clinical data from these two groups were compared, including best visual acuity, refraction, axial length, and electroretinography., Results: The mean amplitudes of rod b-wave, maximum a-wave, maximum b-wave, cone a-wave, and cone b-wave of patients with eoHM were 179 ± 72 μv, -158 ± 63 μv, 345 ± 105 μv, -20 ± 11 μv, and 42 ± 21 μv, respectively, whereas those of patients with loHM were 252 ± 77 μv, -235 ± 60 μv, 464 ± 65 μv, -36 ± 9 μv, and 104 ± 26 μv, respectively (p < 0.001). Patients with eoHM had significantly reduced responses of cones and rods, especially cones, as compared with patients with loHM. The cone-rod responses in patients with loHM were within normal range., Conclusions: The findings suggest that cone-rod dysfunction may be a sign for eoHM compared with loHM.

Purpose: To evaluate retinal structural and functional abnormalities in a patient with acute macular neuroretinopathy., Methods: An adaptive optics scanning light ophthalmoscope was used to image the photoreceptor mosaic and assess rod and cone structure. Spectral-domain optical coherence tomography was used to examine retinal lamination. Microperimetry was used to assess function across the macula., Results: Microperimetry showed reduced function of localized areas within retinal lesions corresponding to subjective scotomas. Spectral-domain optical coherence tomography imaging revealed attenuation of two outer retinal bands typically thought to reflect photoreceptor structure. Adaptive optics scanning light ophthalmoscope images of the photoreceptor mosaic revealed a heterogeneous presentation within these lesions. There were areas containing non-waveguiding cones and other areas of decreased cone density where the remaining rods had expanded to fill in the vacant space. Within these lesions, cone densities were shown to be significantly lower than eccentricity-matched areas of normal retina, as well as accepted histologic measurements. A 6-month follow-up revealed no change in rod or cone structure., Conclusion: Imaging of acute macular neuroretinopathy using an adaptive optics scanning light ophthalmoscope shows a preferential disruption of cone photoreceptor structure within the region of decreased retinal sensitivity (as measured by microperimetry). Adaptive optics-based imaging tools provide a noninvasive way to assess photoreceptor structure at a level of detail that is not resolved by use of conventional spectral-domain optical coherence tomography or other clinical measures.

Purpose: To describe a distinctive foveal cavitation as seen by spectral-domain optical coherence tomography in certain cone dysfunction syndromes., Methods: Observational case series. Patients were evaluated by dilated fundus examination, fundus photography, fundus autofluorescence, full-field electroretinogram, multifocal electroretinogram, spectral-domain optical coherence tomography, color vision testing, fluorescein angiography, Goldmann visual field testing, and molecular genetic analysis., Results: We present eight patients with foveal cavitation in association with presumed cone dysfunction. This was characterized on spectral-domain optical coherence tomography by a gap in the subfoveal outer segment layer without more diffuse retinal thinning. There were 5 patients of age 10 years to 27 years and 3 patients of age 49 years to 52 years, with a 1.5- to 38-year history of bilateral visual loss. A small foveal oval-shaped area of reduced foveal fundus autofluorescence, surrounded by increased fundus autofluorescence, was seen in the younger patients, and a broad circle of increased fundus autofluorescence in the older patients. The multifocal electroretinogram always showed central amplitude reduction, but there were varying degrees of cone dysfunction on full-field electroretinogram. There were mild abnormalities on desaturated color vision testing. The family history was noncontributory in all cases. None of the cases were congenital. ABCA4 gene mutations were identified in three of five patients tested; CNGB3 testing was negative in these patients., Conclusion: Cone dysfunction syndromes typically show retinal thinning on optical coherence tomography imaging, although several case reports have noted focal outer retinal loss. Our case series shows that a distinctive optical coherence tomography finding, foveal cavitation, may be a clue to cone dysfunction syndromes, but is not specific to any one hereditary disorder or age group.

Purpose: To establish adaptive optics scanning laser ophthalmoscopy as a method to detect and characterize microscopic signs of diabetic retinopathy in capillaries and cone photoreceptors in the parafovea., Methods: Recently, adaptive optics scanning laser ophthalmoscope (AOSLO) has enabled noninvasive assessment of photoreceptors, capillaries, and leukocytes in the retinas of live human subjects. Repeated application of AOSLO imaging along with comparison to fluorescein angiography was used to track individual capillaries near the foveal avascular zone (FAZ) from one eye affected with severe non-proliferative diabetic retinopathy. Fluorescein angiography was used to identify clinical signs of diabetic retinopathy, such as microaneurysms and intraretinal microvascular abnormalities, and corresponding regions were imaged and assessed using the AOSLO. In addition, the structural integrity of photoreceptors and the spatial distribution of leukocytes around the parafoveal capillary network were quantitatively assessed., Results: Capillaries and cone photoreceptors were visualized using the AOSLO without the use of injected contrast agents. Although the majority of capillaries were stable over a period of 16 months, one capillary at the edge of the FAZ dropped out, leading to a small but significant increase in FAZ size. Longitudinal assessment of the capillaries also showed microaneurysm formation and disappearance as well as the formation of tiny capillary bends similar in appearance to intraretinal microvascular abnormalities. The leukocytes in the capillary network were found to preferentially travel through the same routes in all four visits, suggesting that these channels are robust against small changes to the surrounding capillaries. In this eye, cone photoreceptor spacing was increased in the fovea when compared with normal data but stable across all visits., Conclusions: AOSLO imaging can be used to longitudinally track capillaries, leukocytes, and photoreceptors in diabetic retinopathy. Capillary changes that can be detected include dropout of individual capillaries as well as formation and disappearance of microaneurysms.

Purpose: To determine the anatomical morphology of Stage 1-A impending macular holes characterized by a yellow spot using spectral-domain optical coherence tomography to study the fellow eyes of patients diagnosed with a full-thickness macular hole or eyes with a typical yellow spot with metamorphopsia., Methods: Prospective observational case series of 45 patients with a full-thickness macular hole or a foveolar yellow spot with metamorphopsia. Visual acuity assessment, biomicroscopic examination, and spectral-domain optical coherence tomography were performed. Clinical ophthalmologic examinations were repeated, including spectral-domain optical coherence tomography, in the eyes with a foveolar yellow spot at 1-month interval., Results: We examined 43 fellow eyes of 43 patients with a macular hole and 2 eyes of 2 patients with a foveolar yellow spot. Five fellow eyes had a yellow spot. Spectral-domain optical coherence tomography clearly showed the reflectivity of the perifoveal posterior vitreous detachment with vitreofoveal adhesion in the 7 eyes with a yellow spot; the foveal microstructure had a triangular foveolar detachment of the cone outer segment tip line, of which only 2 eyes (29%) had foveal splits during the observational period, 3 eyes (43%) had a foveal perpendicular line, and 4 eyes (57%) showed progression to vitreofoveal separation before the development of inner splits or pseudocysts. In those 7 eyes, the 2 eyes (29%) with foveal splits progressed to a full-thickness macular hole. The 38 fellow eyes without a yellow spot had no foveolar detachment., Conclusion: The foveolar detachment of the cone outer segment tip line might be responsible for the yellow spot seen in Stage 1-A macular holes.

The human retina is a uniquely accessible tissue. Tools like scanning laser ophthalmoscopy and spectral domain-optical coherence tomography provide clinicians with remarkably clear pictures of the living retina. Although the anterior optics of the eye permit such non-invasive visualization of the retina and associated pathology, the same optics induce significant aberrations that obviate cellular-resolution imaging in most cases. Adaptive optics (AO) imaging systems use active optical elements to compensate for aberrations in the optical path between the object and the camera. When applied to the human eye, AO allows direct visualization of individual rod and cone photoreceptor cells, retinal pigment epithelium cells, and white blood cells. AO imaging has changed the way vision scientists and ophthalmologists see the retina, helping to clarify our understanding of retinal structure, function, and the etiology of various retinal pathologies. Here, we review some of the advances that were made possible with AO imaging of the human retina and discuss applications and future prospects for clinical imaging.

Purpose: The purpose of this study was to characterize the clinical, electrophysiologic, and genetic features in "cone dystrophy with supernormal rod electroretinogram (ERG).", Methods: Twenty-four cases between 5 and 59 years of age were ascertained. Full-field ERGs, incorporating the international standards, were used to derive intensity-ERG response functions. ON-OFF ERGs were performed. Fundus autofluorescence imaging was performed on 15 subjects. Deoxyribonucleic acid was available in 18 cases and was screened for a mutation in KCNV2., Results: Photophobia and nyctalopia were common. Autofluorescence was variable but often showed a ring-like area of high density that in middle-aged individuals, usually surrounded by an area of macular retinal pigment epithelial atrophy. Scotopic ERG amplitudes overlapped with the normal range but had characteristic a- and b-wave intensity-response functions; all had a broadened a-wave to the brightest flash. Photopic ERGs were abnormal; there was a delay in some ON and most OFF responses. Mutations in KCNV2 were detected in 18 cases, including 4 with novel mutations., Conclusion: Individuals with mutations in KCNV2 manifest a wide range of macular and autofluorescence abnormalities. A ring-like area of parafoveal high density autofluorescence is common. ERG amplitudes are variable, but the intensity-ERG response functions and bright flash ERG waveforms are pathognomonic.

Background: Spinocerebellar ataxia type 7 (SCA7) is a progressive ataxia that is unique among inherited ataxias in having a high prevalence of retinal photoreceptor abnormalities. However, the ophthalmic features and their relationship to the neurologic features of SCA7 have not been widely reported. The goal of this study was to provide increased documentation., Methods: The medical records of 10 consecutive patients with SCA7 examined in the Neuro-Ophthalmology Clinic at Kresge Eye Institute between 2000 and 2008 were reviewed retrospectively. Each patient underwent a standardized ophthalmologic and neurologic examination. Some patients also underwent electroretinography (ERG). Eight patients had genetically confirmed disease and 2 patients had presumptive SCA7 based on their clinical presentation. Patients were excluded if they had visual loss or ataxia due to other causes., Results: Nine patients reported visual symptoms at presentation, including hemeralopia, photophobia, dyschromatopsia, and blurred vision. In 3 of these patients, the visual symptoms had preceded the onset of ataxic symptoms. Visual acuity was abnormal in all patients at presentation. Four patients with visual dysfunction had normal or minimally abnormal macular pigmentary changes, but all patients had abnormal electroretinograms (ERGs) showing primarily cone dysfunction. The severity of visual loss and the severity of ataxia were frequently discordant., Conclusions: Based on this study, patients with SCA7 often have visual symptoms that may precede, accompany, or follow the onset of ataxic symptoms. The severity of vision loss and ataxia may be discordant. Ophthalmoscopic evidence of macular abnormalities may be scant, but results of ERG will always be abnormal. This information may assist in earlier and more cost-effective diagnosis and permit more effective patient counseling.

Background: New technology allows more precise definition of structural alterations of all retinal layers although it has not been used previously in cases of optic disc drusen., Methods: Using Stratus and Fourier domain (FD) optical coherence tomography (OCT) and adaptive optics (AO) through a flood-illuminated fundus camera, we studied the retinas of a patient with long-standing optic disc drusen and acute visual loss at high altitude attributed to ischemic optic neuropathy., Results: Stratus OCT and FD-OCT confirmed severe thinning of the retinal nerve fiber layer (RNFL). FD-OCT revealed disturbances in the photoreceptor layer heretofore not described in optic disc drusen patients. AO confirmed the FD-OCT findings in the photoreceptor layer and also showed reduced cone density at retinal locations associated with reduced visual sensitivity., Conclusions: Based on this study, changes occur not only in the RNFL but also in the photoreceptor layer in optic nerve drusen complicated by ischemic optic neuropathy. This is the first reported application of FD-OCT and the AO to this condition. Such new imaging technology may in the future allow monitoring of disease progression more precisely and accurately.

Purpose: To present ocular fundus images in a patient with enhanced S-cone syndrome by scanning laser ophthalmoscopy. A 34-year-old Japanese woman whose parents were consanguineous showed mismatched electroretinographic responses to photopically balanced single-flash stimuli, with a larger signal to blue light than to red light. The central macula lacked a foveal reflex, and the surface was dull. Yellowish flecks and retinal pigment epithelium atrophy were evident in a ring at and around the vascular arcades. Faint black pigmentation was deposited in the mid peripheral retina., Methods: The ocular fundus of the patient was observed by scanning laser ophthalmoscopy with the use of an argon blue laser (wavelength, 488 nm), a helium-neon laser (633 nm), and an infrared laser (780 nm)., Results: The argon blue laser showed numerous black spots of pigment, which were observed as faint pigmentation by conventional ophthalmoscopy. The spots were more enhanced with the argon blue laser than with the helium-neon laser. The white spots, which corresponded to the yellowish flecks in a ring at and around the vascular arcades, were more enhanced with the helium-neon laser than with the argon blue or infrared laser. Hypopigmentation of the retinal pigment epithelium was best shown with the infrared laser., Conclusion: An abnormality of the retinal structure in enhanced S-cone syndrome may exist in the inner and outer retinal levels, in at least some patients.

Purpose: The effect of form deprivation myopia (FDM) on cone photoreceptor function was investigated., Methods: Photopic electroretinogram (ERG) a-waves were recorded from control and form-deprived eyes of chickens. Cone-generated P3 responses were derived from the leading edge of ERG a-waves using an analytical expression derived from a quantitative model of phototransduction. The parameters obtained were the maximum cone P3 response (RmaxP3), sensitivity (S), and delay (t(d))., Results: P3 response sensitivity is significantly higher in form-deprived eyes, at lower retinal irradiances. At higher flash intensities, in form-deprived eyes, P3 response sensitivity declines at a significantly greater rate, per unit increase in retinal irradiance, than in control eyes. Visual deprivation does not significantly affect RmaxP3 or t(d)., Conclusions: Hypotheses to explain the altered cone photoreceptor sensitivity in form-deprived eyes are proposed. Changes in the biochemistry of phototransduction, or intrinsic geometric and physical attributes of photoreceptors or their waveguide modal properties, could account for the findings.

Our objective was to describe and expand the clinical spectrum of a rarely detected, previously reported photoreceptor disorder restricted to the foveal cones. Three patients with bilaterally decreased acuity and hemeralopia were examined to exclude a structural, vascular, inflammatory, or degenerative process. Each patient underwent a full neuroophthalmic examination, including full-field and focal cone electroretinogram (ERG). All three patients had normal-appearing fundi, mild dyschromatopsia, central or paracentral visual field depressions, normal full-field photopic and scotopic ERGs, and markedly reduced focal, foveal cone ERG responses. One patient had a ring scotoma and an asymptomatic family member with abnormal full-field and focal cone ERG. The syndrome of acquired foveal cone dysfunction presents as a bilateral, painless, progressive central visual loss with minimal or absent fundus changes. It eludes diagnosis until focal, foveal cone ERG is performed.

Purpose: To determine the physical dimensions and location of the cone in keratoconic corneas from videokeratoscopic height data., Methods: Corneal height date from keratoconus patients are obtained with a commercial videokeratoscope and decomposed into the set of orthogonal Zernike polynomials. The low-order Zernike terms are removed from the height data to expose the cone. The location of the peak of the cone and the cone's height and lateral dimensions are measured from the residual height data. This technique is compared to previous dioptric power-based methods of locating the cone., Results: The corneal protrusion due to keratoconus takes on a variety of shapes and locations. These dimensions are easily measured with the Zernike decomposition technique and provide more detailed and accurate information regarding the cone than dioptric power data., Conclusions: The proposed method for quantifying cone dimensions and locale in keratoconic corneas provides practical and detailed information which may be useful in tracking the progression of the disease, contact lens fitting, and surgical planning.