PHOTORECEPTOR INNER SEGMENT MORPHOLOGY IN BEST VITELLIFORM MACULAR DYSTROPHY.

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.

Outer retinal structure after closed-globe blunt ocular trauma.

PURPOSE: To evaluate outer retinal structural abnormalities in patients with visual deficits after closed-globe blunt ocular trauma. METHODS: Nine subjects with visual complaints after closed-globe blunt ocular trauma were examined between 1 month after trauma and 6 years after trauma. Spectral domain optical coherence tomography was used to assess the outer retinal architecture, whereas adaptive optics scanning light ophthalmoscopy was used to analyze the photoreceptor mosaic integrity. RESULTS: Visual deficits ranged from central scotomas to decreased visual acuity. Spectral domain optical coherence tomography defects included focal foveal photoreceptor lesions, variable attenuation of the interdigitation zone, and mottling of the outer segment band, with one subject having normal outer retinal structure. Adaptive optics scanning light ophthalmoscopy revealed disruption of the photoreceptor mosaic in all subjects, variably manifesting as foveal focal discontinuities, perifoveal hyporeflective cones, and paracentral regions of selective cone loss. CONCLUSION: We observe persistent outer retinal disruption in subjects with visual complaints after closed-globe blunt ocular trauma, albeit to a variable degree. Adaptive optics scanning light ophthalmoscopy imaging allows the assessment of photoreceptor structure at a level of detail not resolvable using spectral domain optical coherence tomography or other current clinical imaging tools. Multimodal imaging seems to be useful in revealing the cause of visual complaints in patients after closed-globe blunt ocular trauma. Future studies are needed to better understand how photoreceptor structure changes longitudinally in response to various traumas.

Cone structure in subjects with known genetic relative risk for AMD.

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.

A Prospective, Observational, Non-interventional Clinical Study of Participants With Choroideremia: The NIGHT Study.

PURPOSE: The NIGHT study aimed to assess the natural history of choroideremia (CHM), an X-linked inherited chorioretinal degenerative disease leading to blindness, and determine which outcomes would be the most sensitive for monitoring disease progression. DESIGN: A prospective, observational, multicenter cohort study. METHODS: Males aged ≥18 years with genetically confirmed CHM, visible active disease within the macular region, and best-corrected visual acuity (BCVA) ≥34 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline were assessed for 20 months. The primary outcome was the change in BCVA over time at Months 4, 8, 12, 16, and 20. A range of functional and anatomical secondary outcome measures were assessed up to Month 12, including retinal sensitivity, central ellipsoid zone (EZ) area, and total area of fundus autofluorescence (FAF). Additional ocular assessments for safety were performed. RESULTS: A total of 220 participants completed the study. The mean BCVA was stable over 20 months. Most participants (81.4% in the worse eye and 77.8% in the better eye) had change from baseline > -5 ETDRS letters at Month 20. Interocular symmetry was low overall. Reductions from baseline to Month 12 were observed (worse eye, better eye) for retinal sensitivity (functional outcome; -0.68 dB, -0.48 dB), central EZ area (anatomical outcome; -0.276 mm2, -0.290 mm2), and total area of FAF (anatomical outcome; -0.605 mm2, -0.533 mm2). No assessment-related serious adverse events occurred. CONCLUSIONS: Retinal sensitivity, central EZ area, and total area of FAF are more sensitive than BCVA in measuring the natural progression of CHM.

Prophylactic antibiotic use after intravitreal injection: effect on endophthalmitis rate.

PURPOSE: Endophthalmitis after intravitreal injection is a serious complication. There are limited data to support the use of postinjection antibiotics to prevent endophthalmitis. Current endophthalmitis rates after intravitreal injection in the literature are based on studies where patients routinely received postinjection antibiotics. This study retrospectively compares the rate of endophthalmitis in a cohort of patients receiving postinjection antibiotics with that in a group that does not. METHODS: A retrospective chart review was performed comparing a 12-month period where patients received postinjection topical antibiotics for several days after intravitreal injection with the next 12-month period where no postinjection topical antibiotics were used. Cases of suspected endophthalmitis after intravitreal injection during this period were identified and reviewed. RESULTS: The rate of clinically suspected endophthalmitis in the cohort of patients receiving postinjection antibiotics after intravitreal injection and that in the cohort that did not was 0.22% and 0.20%, respectively. One culture-positive case was found overall. The difference between the 2 groups is not statistically significant (P = 0.75). CONCLUSION: The rate of endophthalmitis after intravitreal injections administered in a clinical practice setting when aseptic technique is used is similar with or without the use of postinjection antibiotics.

Examining Whether AOSLO-Based Foveal Cone Metrics in Achromatopsia and Albinism Are Representative of Foveal Cone Structure.

Purpose: Adaptive optics scanning light ophthalmoscopy (AOSLO) imaging in patients with achromatopsia (ACHM) and albinism is not always successful. Here, we tested whether optical coherence tomography (OCT) measures of foveal structure differed between patients for whom AOSLO images were either quantifiable or unquantifiable. Methods: The study included 166 subjects (84 with ACHM; 82 with albinism) with previously acquired OCT scans, AOSLO images, and best-corrected visual acuity (BCVA, if available). Foveal OCT scans were assessed for outer retinal structure, outer nuclear layer thickness, and hypoplasia. AOSLO images were graded as quantifiable if a peak cone density could be measured and/or usable if the location of peak density could be identified and the parafoveal mosaic was quantifiable. Results: Forty-nine percent of subjects with ACHM and 57% of subjects with albinism had quantifiable AOSLO images. Older age and better BCVA were found in subjects with quantifiable AOSLO images for both ACHM (P = 0.0214 and P = 0.0276, respectively) and albinism (P = 0.0073 and P < 0.0004, respectively). There was a significant trend between ellipsoid zone appearance and ability to quantify AOSLO (P = 0.0028). In albinism, OCT metrics of cone structure did not differ between groups. Conclusions: Previously reported AOSLO-based cone density measures in ACHM may not necessarily reflect the degree of remnant cone structure in these patients. Translational Relevance: Until AOSLO is successful in all patients with ACHM and albinism, the possibility of the reported data from a particular cohort not being representative of the entire population remains an important issue to consider when interpreting results from AOSLO studies.

Retinal Toxicity in a Patient on Pentosan Polysulfate Sodium.

Pentosan Polysulfate Sodium (PPS) is commonly used in the treatment of interstitial cystitis/bladder pain syndrome. Recently there have been reported cases of retinal toxicity associated with long-term PPS use. We present a case of a 42-year-old female taking PPS for the last 10 years who was found to have signs of retinal toxicity, but was completely asymptomatic. PPS was discontinued after these retinal findings were discovered.

Prevalence and Severity of Artifacts in Optical Coherence Tomographic Angiograms.

Importance: Artifacts can affect optical coherence tomographic angiography (OCTA) images and may be associated with misinterpretation of OCT scans in both clinical trials and clinical settings. Objectives: To identify the prevalence and type of artifacts in OCTA images associated with quantitative output and to analyze the role of proprietary quality indices in establishing image reliability. Design, Setting, and Participants: This cross-sectional study evaluated baseline OCTA images acquired in multicenter clinical trials and submitted to the Fundus Photograph Reading Center in Madison, Wisconsin, between January 1, 2016, and December 31, 2018. Images were captured using the 3 mm × 3 mm and/or 6 mm × 6 mm scan protocol with commercially available OCTA systems. Artifacts, including decentration, segmentation error, movement, blink, refraction shift, defocus, shadow, Z offset, tilt, and projection, were given a severity grade based on involvement of cross-sectional OCT and area of OCT grid affected. Main Outcomes and Measures: Prevalence and severity of OCTA artifacts and area under the receiver operating characteristic curve (AUC) of quality indices with image reliability. Results: A total of 406 OCTA images from 234 eyes were included in this study, of which 221 (54.4%) were 6 mm × 6 mm scans and 185 (45.6%) were 3 mm × 3 mm scans. At least 1 artifact was documented in 395 images (97.3%). Severe artifacts associated with the reliability of quantitative outputs were found in 217 images (53.5%). Shadow (26.9% [109 images]), defocus (20.9% [85 images]), and movement (16.0% [65 images]) were the 3 most prevalent artifacts. Prevalence of artifacts did not vary with the imaging system used or with the scan protocol; however, the type of artifacts varied. Commercially recommended quality index thresholds had an AUC of 0.80 to 0.83, sensitivity of 97% to 99%, and specificity of 37% to 41% for reliable images. Conclusions and Relevance: Findings from this study suggest that artifacts associated with quantitative outputs on commercially available OCTA devices are highly prevalent and that identifying common artifacts may require correlation with the angiogram and cross-sectional OCT scans. Knowledge of these artifacts and their implications for OCTA indices appears to be warranted for more accurate interpretation of OCTA images.

Increased incidence of sterile endophthalmitis after intravitreal triamcinolone acetonide in spring 2006.

PURPOSE: To compare the incidence of sterile endophthalmitis after intravitreal triamcinolone acetonide injections during a 6 month period in 2006 to the same period in 2005 and determine the incidence after switching to intravitreal preservative-free triamcinolone acetonide. METHODS: Retrospective multicenter interventional case series in which patients receiving intravitreal triamcinolone acetonide at three institutions from March 2005 to August 2005 and from March 2006 to August 2006 and intravitreal preservative-free triamcinolone acetonide from late summer 2006 through February 2007 were reviewed for the development of sterile endophthalmitis. RESULTS: From March 2005 to August 2005, the rate of sterile endophthalmitis was 0% at all institutions. From March 2006 to August 2006, a statistically significant increase in sterile endophthalmitis was seen at all institutions with frequencies of 3.5% to 6.3% (P < 0.001). With transition to preservative-free triamcinolone acetonide, sterile endophthalmitis over the next 6 months decreased to 0% at two sites and to 2.5% (from 5.5%) at the third institution (P < 0.009). CONCLUSIONS: A statistically significant increase in the rate of sterile endophthalmitis after intravitreal triamcinolone acetonide was seen in a 6 month period in 2006 when compared with the same period in 2005. Transition to preservative-free triamcinolone acetonide produced a frequency of sterile endophthalmitis similar to 2005.

Comparison of intravitreal bevacizumab followed by ranibizumab for the treatment of neovascular age-related macular degeneration.

PURPOSE: To compare outcomes after switching from intravitreal bevacizumab (Avastin) to ranibizumab (Lucentis) in patients with neovascular age-related macular degeneration (AMD). METHODS: A retrospective review was performed of patients with neovascular AMD who were switched from treatment with intravitreal bevacizumab to intravitreal ranibizumab once ranibizumab became commercially available. All reviewed patients had at least three bevacizumab injections before being switched to ranibizumab. The treatment outcomes included comparisons of visual acuity and dosing frequency while receiving both drugs. RESULTS: Eighty-four eyes met the inclusion criteria. Mean baseline visual acuity was 20/100. Mean duration of bevacizumab treatment was 7.1 months followed by 7.3 months with ranibizumab (P = 0.68). Best-obtained visual acuity during treatment was 20/63 with bevacizumab and 20/63 with ranibizumab (P = 0.5). Last mean visual acuity after receiving bevacizumab at the time of the first ranibizumab injection was 20/80. Mean visual acuity at the last ranibizumab follow-up visit was 20/80 (P = 0.49). Mean injection rates per month while receiving bevacizumab and ranibizumab were 0.66 (P = 0.98). CONCLUSION: In this subset of patients with neovascular AMD switched from bevacizumab to ranibizumab therapy, there were no apparent differences in visual acuity outcomes or injection rates. Larger prospective studies are under way to directly compare these drugs for the treatment of neovascular AMD.

Macular spatial distribution of preserved autofluorescence in patients with choroideremia.

BACKGROUND/AIMS: To better understand the pattern of degeneration progression in cases with choroideremia. METHODS: A cohort of genotypically confirmed choroideremia cases who underwent optical coherence tomography (OCT) and fundus autofluorescence (FAF) imaging was studied. Using HEYEX review software, the foveal centre was marked on FAF images under guidance of corresponding OCT images, followed by application of an ETDRS grid. The boundaries of preserved autofluorescence (AF) were manually segmented in each individual ETDRS subfield. The regional distribution of preserved AF was assessed by comparing its area among the various subfields. RESULTS: A total of 168 eyes from 84 choroideremia cases were enrolled. There was a statistically significant difference in the amount of preserved AF area between inner subfields as determined by one-way analysis of variance (F (3,668)=9.997, p<0.001) and also between outer subfields (F (3,668)=8.348, p<0.001). A Tukey posthoc test revealed that the preserved AF area in the nasal subfields in both the inner and outer subfields was significantly smaller compared with analogue subfields. CONCLUSION: The asymmetric spatial distribution of preserved AF in choroideremia (corresponding to the stellate shaped nature of these regions) suggests that the progression of degeneration has directional preference.

Assessing photoreceptor structure in patients with traumatic head injury.

OBJECTIVE: Previous work using adaptive optics scanning light ophthalmoscopy (AOSLO) imaging has shown photoreceptor disruption to be a common finding in head and ocular trauma patients. Here an expanded trauma population was examined using a novel imaging technique, split-detector AOSLO, to assess remnant cone structure in areas with significant disruption on confocal AOSLO imaging and to follow photoreceptor changes longitudinally. METHODS AND ANALYSIS: Eight eyes from seven subjects with head and/or ocular trauma underwent imaging with spectral domain optical coherence tomography, confocal AOSLO and split-detector AOSLO to assess foveal and parafoveal photoreceptor structure. RESULTS: Confocal AOSLO imaging revealed hyporeflective foveal regions in two of eight eyes. Split-detector imaging within the hyporeflective confocal areas showed both remnant and absent inner-segment structure. Both of these eyes were imaged longitudinally and showed variation of the photoreceptor mosaic over time. Four other eyes demonstrated subclinical regions of abnormal waveguiding photoreceptors on multimodal AOSLO imagery but were otherwise normal. Two eyes demonstrated normal foveal cone packing without disruption. CONCLUSION: Multimodal imaging can detect subtle photoreceptor abnormalities not necessarily detected by conventional clinical imaging. The addition of split-detector AOSLO revealed the variable condition of inner segments within confocal photoreceptor disruption, confirming the usefulness of dual-modality AOSLO imaging in assessing photoreceptor structure and integrity. Longitudinal imaging demonstrated the dynamic nature of the photoreceptor mosaic after trauma. Multimodal imaging with dual-modality AOSLO improves understanding of visual symptoms and photoreceptor structure changes in patients with head and ocular trauma.

Intraobserver Repeatability and Interobserver Reproducibility of Ellipsoid Zone Measurements in Retinitis Pigmentosa.

PURPOSE: To examine repeatability and reproducibility of ellipsoid zone (EZ) width measurements in patients with retinitis pigmentosa (RP) using a longitudinal reflectivity profile (LRP) analysis. METHODS: We examined Bioptigen optical coherence tomography (OCT) scans from 48 subjects with RP or Usher syndrome. Nominal scan lengths were 6, 7, or 10 mm, and the lateral scale of each scan was calculated using axial length measurements. LRPs were generated from OCT line scans, and the peak corresponding to EZ was manually identified using ImageJ. The locations at which the EZ peak disappeared were used to calculate EZ width. Each scan was analyzed twice by each of two observers, who were masked to their previous measurements and those of the other observer. RESULTS: On average, horizontal width (HW) was significantly greater than vertical width (VW), and there was high interocular symmetry for both HW and VW. We observed excellent intraobserver repeatability with intraclass correlation coefficients (ICCs) ranging from 0.996 to 0.998 for HW and VW measurements. Interobserver reproducibility was also excellent for both HW (ICC = 0.989; 95% confidence interval [CI] = 0.983-0.995) and VW (ICC = 0.991; 95% CI = 0.985-0.996), with no significant bias observed between observers. CONCLUSIONS: EZ width can be measured using LRPs with excellent repeatability and reproducibility. Our observation of greater HW than VW is consistent with previous observations in RP, though the reason for this anisotropy remains unclear. TRANSLATIONAL RELEVANCE: We describe repeatability and reproducibility of a method for measuring EZ width in patients with RP or Usher syndrome. This approach could facilitate measurement of retinal band thickness and/or intensity.

Multimodal Imaging of Photoreceptor Structure in Choroideremia.

PURPOSE: Choroideremia is a progressive X-linked recessive dystrophy, characterized by degeneration of the retinal pigment epithelium (RPE), choroid, choriocapillaris, and photoreceptors. We examined photoreceptor structure in a series of subjects with choroideremia with particular attention to areas bordering atrophic lesions. METHODS: Twelve males with clinically-diagnosed choroideremia and confirmed hemizygous mutations in the CHM gene were examined. High-resolution images of the retina were obtained using spectral domain optical coherence tomography (SD-OCT) and both confocal and non-confocal split-detector adaptive optics scanning light ophthalmoscope (AOSLO) techniques. RESULTS: Eleven CHM gene mutations (3 novel) were identified; three subjects had the same mutation and one subject had two mutations. SD-OCT findings included interdigitation zone (IZ) attenuation or loss in 10/12 subjects, often in areas with intact ellipsoid zones; RPE thinning in all subjects; interlaminar bridges in the imaged areas of 10/12 subjects; and outer retinal tubulations (ORTs) in 10/12 subjects. Only split-detector AOSLO could reliably resolve cones near lesion borders, and such cones were abnormally heterogeneous in morphology, diameter and density. On split-detector imaging, the cone mosaic terminated sharply at lesion borders in 5/5 cases examined. Split-detector imaging detected remnant cone inner segments within ORTs, which were generally contiguous with a central patch of preserved retina. CONCLUSIONS: Early IZ dropout and RPE thinning on SD-OCT are consistent with previously published results. Evidence of remnant cone inner segments within ORTs and the continuity of the ORTs with preserved retina suggests that these may represent an intermediate state of retinal degeneration prior to complete atrophy. Taken together, these results supports a model of choroideremia in which the RPE degenerates before photoreceptors.

Assessing Photoreceptor Structure in Retinitis Pigmentosa and Usher Syndrome.

PURPOSE: The purpose of this study was to examine cone photoreceptor structure in retinitis pigmentosa (RP) and Usher syndrome using confocal and nonconfocal split-detector adaptive optics scanning light ophthalmoscopy (AOSLO). METHODS: Nineteen subjects (11 RP, 8 Usher syndrome) underwent ophthalmic and genetic testing, spectral-domain optical coherence tomography (SD-OCT), and AOSLO imaging. Split-detector images obtained in 11 subjects (7 RP, 4 Usher syndrome) were used to assess remnant cone structure in areas of altered cone reflectivity on confocal AOSLO. RESULTS: Despite normal interdigitation zone and ellipsoid zone appearance on OCT, foveal and parafoveal cone densities derived from confocal AOSLO images were significantly lower in Usher syndrome compared with RP. This was due in large part to an increased prevalence of non-waveguiding cones in the Usher syndrome retina. Although significantly correlated to best-corrected visual acuity and foveal sensitivity, cone density can decrease by nearly 38% before visual acuity becomes abnormal. Aberrantly waveguiding cones were noted within the transition zone of all eyes and corresponded to intact inner segment structures. These remnant cones decreased in density and increased in diameter across the transition zone and disappeared with external limiting membrane collapse. CONCLUSIONS: Foveal cone density can be decreased in RP and Usher syndrome before visible changes on OCT or a decline in visual function. Thus, AOSLO imaging may allow more sensitive monitoring of disease than current methods. However, confocal AOSLO is limited by dependence on cone waveguiding, whereas split-detector AOSLO offers unambiguous and quantifiable visualization of remnant cone inner segment structure. Confocal and split-detector thus offer complementary insights into retinal pathology.

Correlating Photoreceptor Mosaic Structure to Clinical Findings in Stargardt Disease.

PURPOSE: To demonstrate a method for correlating photoreceptor mosaic structure with optical coherence tomography (OCT) and microperimetry findings in patients with Stargardt disease. METHODS: A total of 14 patients with clinically diagnosed Stargardt disease were imaged using confocal and split-detection adaptive optics scanning light ophthalmoscopy. Cone photoreceptors were identified manually in a band along the temporal meridian. Resulting values were compared to a normative database (n = 9) to generate cone density deviation (CDD) maps. Manual measurement of outer nuclear layer plus Henle fiber layer (ONL+HFL) thickness was performed, in addition to determination of the presence of ellipsoid zone (EZ) and interdigitation zone (IZ) bands on OCT. These results, along with microperimetry data, were overlaid with the CDD maps. RESULTS: Wide variation in foveal structure and CDD maps was seen within this small group. Disruption of ONL+HFL and/or IZ band was seen in all patients, with EZ band preservation in regions with low cone density in 38% of locations analyzed. Normality of retinal lamellar structure on OCT corresponded with cone density and visual function at 50/78 locations analyzed. Outer retinal tubulations containing photoreceptor-like structures were observed in 3 patients. CONCLUSIONS: The use of CDD color-coded maps enables direct comparison of cone mosaic local density with other measures of retinal structure and function. Larger normative datasets and improved tools for automation of image alignment are needed. TRANSLATIONAL RELEVANCE: The approach described facilitates comparison of complex multimodal data sets from patients with inherited retinal degeneration, and can be expanded to incorporate other structural imaging or functional testing.

Clinical Insights Into Foveal Morphology in Albinism.

PURPOSE: A hallmark of albinism is foveal hypoplasia. However, literature suggests variable foveal development. This study evaluates the association between ocular phenotype and foveal morphology to demonstrate the broad structural and functional spectrum. METHODS: Best-corrected visual acuity (BCVA), nystagmus, angle kappa, stereoacuity, iris transillumination, macular melanin presence, foveal avascular zone, and annular reflex were recorded in 14 patients with albinism. Spectral-domain optical coherence tomography provided macular images. RESULTS: The clinical phenotype was broad, with BCVA varying from 20/20 to 20/100. Better BCVA was associated with a preserved foveal avascular zone, annular macular reflex, stereoacuity, and macular melanin. Imaging demonstrated a continuum of foveal development correlating with BCVA. Individuals with a rudimentary pit had normal inner and outer segment lengthening and better BCVA. CONCLUSIONS: The spectrum of ocular structure and visual function in albinism is broad, suggesting a possible diagnosis of albinism in a patient with an even more normal clinical presentation.