Macular Dysfunction Research Articles

Optical Coherence Tomography Split-Spectrum Amplitude-Decorrelation Optoretinography Detects Early Central Cone Photoreceptor Dysfunction in Retinal Dystrophies.

To investigate if split-spectrum amplitude-decorrelation optoretinography (SSADOR) can detect and measure macular cone dysfunction in inherited retinal dystrophies (IRDs). This study was a case series of participants presenting with various IRD pathologies. Participants were recruited from the Ophthalmic Genetics clinic at the Casey Eye Institute from February to August 2023. Multimodal and SSADOR imaging was obtained in all cases. We recruited nine participants, including four with macular dystrophy, one with fundus flavimaculatus, one with cone dystrophy, and three with retinitis pigmentosa. SSADOR decorrelation maps identified areas of cone functional impairment consistent with disease phenotypes. A correlation between the SSADOR signal and retinal sensitivity measured by microperimetry within the central 20° diameter area was observed. Additionally, SSADOR was able to demonstrate a decreased signal in mild cases when microperimetry measurements were still normal but subtle changes were also apparent on structural OCT. SSADOR is sensitive at detecting functional changes in macular cones, even prior to abnormalities in perimetry testing. We highlight the potential benefits of this innovative technology for the early detection of cone dysfunction and their potential contributions to earlier diagnosis and more accurate monitoring of progression. SSADOR is an innovative technology that detects early macular cone function changes, allowing for early diagnosis and precise monitoring of cone dysfunction progression. By serving as a potential clinical trial endpoint, SSADOR facilitates the translation of scientific findings into practical applications, ultimately improving patient care and outcomes.

Shwachman-Diamond syndrome associated with rod-cone dystrophy.

To report a patient with Shwachman-Diamond syndrome and concomitant rod-cone dystrophy who underwent bone marrow transplantation. Retrospective single case report. A female patient with Shwachman-Diamond syndrome was referred to a tertiary hospital to investigate possible pigmentary retinopathy at the age of 16. She described poor night vision and was found to have reduced visual acuity (6/20 right, 6/38 left). Over the ten-year follow-up period, her visual acuity remained relatively stable with no new visual symptoms. Optical coherence tomography revealed progressive, diffuse outer retinal thinning with disruption of the ellipsoid zone, which initially was relatively preserved subfoveally. Fundus autofluorescence images revealed generalised areas of hypoautofluorescence beyond the vascular arcades and a perimacular ring of increased autofluorescence. The flash electroretinogram was in keeping with a severe rod-cone dystrophy. The pattern visual evoked potential was abnormal but detectable indicating macular pathway dysfunction, suggesting encroachment into central macular regions but with some functional preservation. We report a patient with Shwachman-Diamond syndrome with severe early-onset rod-cone dystrophy noted at the age of 16. Slow anatomical progression has been observed over the subsequent ten years, with relative functional macular preservation to support a visual acuity of 6/36 in both eyes.

RP2-Associated X-linked Retinopathy: Clinical Findings, Molecular Genetics, and Natural History in a Large Cohort of Female Carriers

RP2-associated retinopathy typically causes severe early onset retinitis pigmentosa (RP) in affected males. However, there is a scarcity of reports describing the clinical phenotype of female carriers. We tested the hypothesis that RP2 variants manifest in female carriers with a range of functional and anatomic characteristics. Retrospective case series. Females with disease-causing variants in RP2 were identified from investigation of pedigrees affected by RP2 retinopathy. All case notes and results of molecular genetic testing, retinal imaging (fundus autofluorescence imaging, optical coherence tomography (OCT)), and electrophysiology were reviewed. Forty pedigrees were investigated. Twenty-nine pedigrees had obligate carriers or molecularly confirmed female members with recorded relevant history and/or examination. For 8 pedigrees, data were available only from history, with patients reporting affected female relatives with RP in 4 cases and unaffected female relatives in the other 4 cases. Twenty-seven females from 21 pedigrees were examined by a retinal genetics specialist. Twenty-three patients (85%) reported no complaints and had normal vision and 4 patients had RP-associated complaints (15%). Eight patients had normal fundus examination (30%), 10 had a tapetal-like reflex (TLR; 37%), 5 had scattered peripheral pigmentation (19%), and the 4 symptomatic patients had fundus findings compatible with RP (15%). All asymptomatic patients with normal fundus, TLR, or asymptomatic pigmentary changes had a continuous ellipsoid zone on OCT when available. The electroretinograms revealed mild to severe photoreceptor dysfunction in 9 of 11 subjects, often asymmetrical, including 5 with pattern electroretinogram evidence of symmetrical (n = 4) or unilateral (n = 1 subject) macular dysfunction. Most carriers were asymptomatic, exhibiting subclinical characteristics such as TLR and pigmentary changes. However, female carriers of RP2 variants can manifest RP. Family history of affected females with RP does not exclude X-linked disease. The phenotypic spectrum as described herein has prognostic and counselling implications for RP2 carriers and patients.

RBP3-Retinopathy—Inherited High Myopia and Retinal Dystrophy: Genetic Characterization, Natural History, and Deep Phenotyping

To examine the genetic and clinical features and the natural history of RBP3-associated retinopathy. Multi-center international, retrospective, case series of adults and children, with moleculraly confirmed RBP3-asociated retinopathy. The genetic, clinical, and retinal imaging findings, including optical coherence tomography (OCT) and fundus autofluorescence (FAF), were investigated both cross-sectionally and longitudinally. The results of international standard full-field electroretinography (ERG) and pattern electroretinography (PERG) were reviewed. We ascertained 12 patients (5 female and 7 male) from 10 families (4 patients previously reported). Ten novel disease-causing RBP3 variants were identified. Ten patients were homozygous. The mean age (±SD, range) of the group was 21.4 years (±19.1, 2.9-60.5 years) at baseline evaluation. All 12 patients were highly myopic, with a mean spherical equivalent of -16.0D (range, -7.0D to -33.0D). Visual acuity was not significantly different between eyes, and no significant anisometropia was observed. Mean best-corrected visual acuity (BCVA) was 0.48 logMAR (SD, ±0.29; range, 0.2-1.35 logMAR); at baseline. Eleven patients had longitudinal BCVA assessment, with a mean BCVA of 0.46 logMAR after a mean follow-up of 12.6 years. All patients were symptomatic with reduced VA and myopia by the age of 7 years old. All patients had myopic fundi and features in keeping with high myopia on OCT, including choroidal thinning. The 4 youngest patients had no fundus pigmentary changes, with the rest of the patients presenting with a variable degree of mid-peripheral pigmentation and macular changes. FAF showed variable phenotypes, ranging from areas of increased signal to advanced atrophy in older patients. OCT showed cystoid macular edema at presentation in 3 patients, which persisted during follow-up in 2 patients and resolved to atrophy in the third patient. The ERGs were abnormal in 9 of 9 cases, revealing variable relative involvement of rod and cone photoreceptors with additional milder dysfunction post-phototransduction in some. All but 1 patient had PERG evidence of macular dysfunction, which was severe in most cases. This study details the clinical and functional phenotype of RBP3-retinopathy in the largest cohort reported to date. RBP3-retinopathy is a disease characterized by early onset, slow progression over decades, and high myopia. The phenotypic spectrum and natural history as described herein has prognostic and counseling implications. RBP3-related disease should be considered in children with high myopia and retinal dystrophy.

Occult Macular Dysfunction Syndrome: Identification of Multiple Pathologies in a Clinical Spectrum of Macular Dysfunction with Normal Fundus in East Asian Patients: EAOMD Report No. 5.

Occult macular dystrophy (OMD) is the most prevalent form of macular dystrophy in East Asia. Beyond RP1L1, causative genes and mechanisms remain largely uncharacterised. This study aimed to delineate the clinical and genetic characteristics of OMD syndrome (OMDS). Patients clinically diagnosed with OMDS in Japan, South Korea, and China were enrolled. The inclusion criteria were as follows: (1) macular dysfunction and (2) normal fundus appearance. Comprehensive clinical evaluation and genetic assessment were performed to identify the disease-causing variants. Clinical parameters were compared among the genotype groups. Seventy-two patients with OMDS from fifty families were included. The causative genes were RP1L1 in forty-seven patients from thirty families (30/50, 60.0%), CRX in two patients from one family (1/50, 2.0%), GUCY2D in two patients from two families (2/50, 4.0%), and no genes were identified in twenty-one patients from seventeen families (17/50, 34.0%). Different severities were observed in terms of disease onset and the prognosis of visual acuity reduction. This multicentre large cohort study furthers our understanding of the phenotypic and genotypic spectra of patients with macular dystrophy and normal fundus. Evidently, OMDS encompasses multiple Mendelian retinal disorders, each representing unique pathologies that dictate their respective severity and prognostic patterns.

A novel ELOVL4 variant, L168S, causes early childhood-onset Spinocerebellar ataxia-34 and retinal dysfunction: a case report

Spinocerebellar ataxia 34 (SCA34) is an autosomal dominant inherited disease characterized by age-related cerebellar degeneration and ataxia caused by mutations in the Elongation of Very Long Chain Fatty Acid-4 (ELOVL4) gene. The ELOVL4 enzyme catalyzes the biosynthesis of both very long chain saturated fatty acids (VLC-SFA) and very long chain polyunsaturated fatty acids (VLC-PUFA) that are important for neuronal, reproductive, and skin function. Several variants in ELOVL4 have been shown to cause different tissue-specific disorders including SCA34 with or without Erythrokeratodermia Variabilis (EKV), a skin condition characterized by dry, scaly skin, Autosomal Dominant Stargardt-Like Macular Dystrophy (STGD3), and seizures associated with neuro-ichthyotic disorders. What is puzzling is how different mutations in the same gene seem to cause different tissue-specific disorders. To date, no SCA34 patients have presented with both SCA34 and STGD3 pathology that is caused by ELOVL4 variants that cause truncation of ELOVL4. Here, we report a novel case of an early childhood onset and rapidly progressive cerebellar degeneration and retinal dysfunction in a Belgian-Italian girl who developed severe dysarthria and gait problems starting at about 3.5 years of age and progressed to immobility by 4.5 years of age. Brain magnetic resonance imaging (MRI) revealed progressive vermian, cerebellar, cortical atrophy, progressive corpus callosum slimming, and hot cross bun sign visible on the MRI. Ophthalmological examinations also revealed progressive macular dysfunction as measured by electroretinography. Using exome sequencing, we identified a novel heterozygous ELOVL4 variant, c.503 T > C (p. L168S) in the patient. To understand the enzymatic function of this novel ELOVL4 variant and how it alters the levels of VLC-PUFA and VLC-SFA biosynthesis to contribute to cerebellar and retinal dysfunction, we expressed wild-type ELOVL4 or the L168S ELOVL4 variant in cell culture and supplemented the cultures with VLC-PUFA or VLC-SFA precursors. We showed that the L168S ELOVL4 variant is deficient in the biosynthesis of VLC-SFA and VLC-PUFA. Our work suggests that differential depletion of these fatty acids may be a contributing factor to the pathogenic mechanism of SCA34 with or without EKV. Further studies will help further define how the different ELOVL4 variants cause different tissue-specific disorders with variable ages of onset.

Structured light enhanced entoptic stimuli for vision science applications.

The dichroic macular pigment in the Henle fiber layer in the fovea enables humans to perceive entoptic phenomena when viewing polarized blue light. In the standard case of linearly polarized stimuli, a faint bowtie-like pattern known as the Haidinger's brush appears in the central point of fixation. As the shape and clarity of the perceived signal is directly related to the health of the macula, Haidinger's brush has been used as a diagnostic marker in studies of early stage macular degeneration and central field visual dysfunction. However, due to the weak nature of the perceived signal the perception of the Haidinger's brush has not been integrated with modern clinical methods. Recent attempts have been made to increase the strength of the perceived signal by employing structured light with spatially varying polarization profiles. Here we review the advancements with the structured light stimuli and describe the current challenges and future prospects.

CERKL-Associated Retinal Dystrophy: Genetics, Phenotype, and Natural History

To analyze the clinical characteristics, natural history, and genetics of CERKL-associated retinal dystrophy in the largest series to date. Multicenter retrospective cohort study. Forty-seven patients (37 families) with likely disease-causing CERKL variants. Review of clinical notes, ophthalmic images, and molecular diagnosis from 2 international centers. Visual function, retinal imaging, and characteristics were evaluated and correlated. The mean age at the first visit was 29.6± 13.9 years, and the mean follow-up time was 9.1± 7.4 years. The most frequent initial symptom was central vision loss (40%), and the most common retinal feature was well-demarcated areas of macular atrophy (57%). Seventy-seven percent of the participants had double-null genotypes, and 64% had electrophysiological assessment. Among the latter, 53% showed similar severity of rod and cone dysfunction, 27% revealed a rod-cone, 10% a cone-rod, and 10% a macular dystrophy dysfunction pattern. Patients without double-null genotypes tended to have fewer pigment deposits and included a higher proportion of older patients with a relatively mild electrophysiological phenotype. Longitudinal analysis showed that over half of the cohort lost 15 ETDRS letters or more in ≥ 1 eye during the first 5 years of follow-up. The phenotype of CERKL-retinal dystrophy is broad, encompassing isolated macular disease to severe retina-wide involvement, with a range of functional phenotypes, generally not fitting in the rod-cone/cone-rod dichotomy. Disease onset is often earlier, with more severe retinal degenerative changes and photoreceptor dysfunction, in nullizygous cases. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Diagnosis, treatment and monitoring of diabetic eye disease (Update 2023)

Diabetes mellitus can cause diabetic retinopathy, diabetic macular edema, optic neuropathy, cataract or dysfunction of the eye muscles. The incidence of these disorders correlates with disease duration and quality of metabolic control. Regular ophthalmological examinations are needed to prevent sight-threatening advanced stages of diabetic eye diseases.

The value of colour assessment in diagnostic dilemmas

AbstractBackground: When the goal of clinical assessment is to segment, divide, and classify cases into neat discrete boxes it can often be frustrating to encounter cases which do not fit standard diagnosis algorithms. However, such diagnostic dilemmas often provide a valuable insight into the boundaries of current clinical procedures and the potential value psychophysical assessment can provide when used in conjunction with standard diagnosis algorithms. We present such a case involving localized retinal dysfunction that is not fully consistent with signs of either autoimmune retinopathy or occult maculopathy.Methods: Specific visual function loss was investigated in a health 32‐year‐old male with suspected localized retinal dysfunction, affecting the central retina. Blood tests and electro‐diagnostics were carried out after the patient presented with acute onset ‘foggy’ central vision. The working diagnosis from this initial visit was autoimmune retinopathy and oral steroids were prescribed. Following no change in symptoms a year after initially presenting, the patient was referred to City, University of London for bespoke assessments of specific visual functions. These included assessments of central and peripheral red / green (RG) and yellow / blue (YB) colour vision, mesopic visual acuity (VA), functional contrast sensitivity (FCS), rod‐ and cone‐mediated flicker sensitivity, and pupil responses measured using both rod‐ and cone‐enhanced stimuli.Results: The loss of vision affected primarily the central 20° with a mean VA of 6/36 in each eye. Fundus images, fluorescein angiography, and full field electroretinograms (ERGs) were normal, but pattern and focal ERGs were undetectable indicating localized dysfunction in central vision with OCT images showing a disrupted ellipsoid zone in each eye. The patient's mean corpuscular volume was 69 femtoliters, with red cell indices suggestive of thalassemia. Testing at City, University of London confirmed a loss of VA and FCS in the central 10° field, although both VA and FCS depended strongly on light level and were less affected with negative contrast stimuli. A loss of RG and YB colour vision was also measured centrally. Outside the central 10° field EA had almost normal colour and spatial vision. Rod‐ and cone‐mediated, flicker thresholds were elevated, with cone thresholds 10‐fold higher than normal. Pre‐stimulus pupil size, constriction amplitudes and latencies were normal with both centrally presented and peripheral stimuli.Conclusions: Psychophysical measurements in a patient with presumed autoimmune maculopathy showed atypical macular dysfunction that appears to preferentially affect negative contrast stimuli. Despite damage to the retinal mechanisms involved in spatial vision and light adaptation pupil responses remained unaffected. This unusual case highlights the importance of detailed phenotyping in understanding unknown aetiology.

Middle-Inner Macular Layers Dysfunction in a Case of Stellate Foveomacular Retinoschisis Detected by Abnormal Multifocal Photopic Negative Response Recordings.

We describe the macular morpho-functional assessment of a 65-year-old man affected by stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR), studied by visual field, SD-OCT, autofluorescence, full-field electroretinogram (ffERG), multifocal electroretinogram (mfERG) and multifocal Photopic Negative Response (mfPhNR) recordings. The typical presentation consists of the foveal appearance of radial cartwheel pattern for the splitting of the retinal layers at the level of the Henle fiber layer (HFL) and the outer plexiform layer (OPL), perfectly seen by Spectral Domain-Optical Coherence Tomography (SD-OCT). Despite a normal function of the outer retina of the peripheral and central retina evaluated by ffERG and mfERG respectively, we observed a reduced function of the retinal elements involved in the retinoschisis by recording mfPhNR that assesses mainly inner retina function (retinal ganglion cells and their axons). Therefore, it is likely that the observed impaired mfPhNR responses reflect the signaling defects derived from the delaminated middle retina and transmitted to the innermost retinal layers.

Phenotyping of ABCA4 Retinopathy by Machine Learning Analysis of Full-Field Electroretinography.

PurposeBiallelic pathogenic variants in ABCA4 are the commonest cause of monogenic retinal disease. The full-field electroretinogram (ERG) quantifies severity of retinal dysfunction. We explored application of machine learning in ERG interpretation and in genotype–phenotype correlations.MethodsInternational standard ERGs in 597 cases of ABCA4 retinopathy were classified into three functional phenotypes by human experts: macular dysfunction alone (group 1), or with additional generalized cone dysfunction (group 2), or both cone and rod dysfunction (group 3). Algorithms were developed for automatic selection and measurement of ERG components and for classification of ERG phenotype. Elastic-net regression was used to quantify severity of specific ABCA4 variants based on effect on retinal function.ResultsOf the cohort, 57.6%, 7.4%, and 35.0% fell into groups 1, 2, and 3 respectively. Compared with human experts, automated classification showed overall accuracy of 91.8% (SE, 0.169), and 96.7%, 39.3%, and 93.8% for groups 1, 2, and 3. When groups 2 and 3 were combined, the average holdout group accuracy was 93.6% (SE, 0.142). A regression model yielded phenotypic severity scores for the 47 commonest ABCA4 variants.ConclusionsThis study quantifies prevalence of phenotypic groups based on retinal function in a uniquely large single-center cohort of patients with electrophysiologically characterized ABCA4 retinopathy and shows applicability of machine learning. Novel regression-based analyses of ABCA4 variant severity could identify individuals predisposed to severe disease.Translational RelevanceMachine learning can yield meaningful classifications of ERG data, and data-driven scoring of genetic variants can identify patients likely to benefit most from future therapies.

ASSESSMENTS OF MACULAR FUNCTION BY FOCAL MACULAR ELECTRORETINOGRAPHY AND STATIC PERIMETRY IN EYES WITH RETINITIS PIGMENTOSA.

To assess the macular function by focal macular electroretinography and static perimetry in eyes with retinitis pigmentosa. Eighty-eight eyes of 88 retinitis pigmentosa patients were analyzed. The relationships between the focal macular electroretinography components and the mean deviations (MDs) of the Humphrey Field Analyzer 10-2 were determined. Spectral-domain optical coherence tomography was used to determine the integrity of the ellipsoid zone (EZ) and the interdigitation zone. Forward-backward stepwise regression analyses showed that the amplitudes (r = 0.45, P < 0.01) and implicit times (r = -0.29, P < 0.01) of the b-waves were significantly correlated with the MDs. Some of the eyes had reduced b-wave amplitudes (<1.0 µ V) and disrupted interdigitation zone, despite having a better MD (≥ -10.0 dB) and intact EZ. Subgroup analyses of eyes with better MD (≥ -10.0 dB) showed that the EZ width was correlated with the MDs but not with the b-wave amplitude. The thickness of the EZ-retinal pigment epithelium as an alternative indicator of interdigitation zone was correlated with the b-wave amplitude (r = 0.32, P = 0.04) but not with the MDs (r = -0.10, P = 0.53). The fact that the focal macular electroretinography amplitudes are reduced before the shortening of the EZ in the early stage of retinitis pigmentosa indicates that the focal macular electroretinography amplitudes are an earlier indicator of macular dysfunction than the Humphrey Field Analyzer 10-2 findings.

This issue of ACTA

This issue of ACTA

Three cases of macular hole that occurred in inferior scleral staphyloma associated with tilted disc syndrome: a case series

BackgroundThe objective is to examine the clinical characteristics of three patients with macular hole that occurred in inferior posterior staphyloma associated with tilted disc syndrome.Case presentationsThis study involved three eyes of three Japanese female patients (mean age 76.0 years, range 73–84 years) with macular hole occurring in inferior posterior staphyloma associated with tilted disc syndrome. One of the three eyes was slightly myopic, while the other two eyes were highly myopic. In all three eyes, the macular hole was found to be located in or near the margin of the inferior posterior staphyloma. In one eye, the extent of retinoschisis was rather broad in the margin of the macular hole, and another eye had a history of treatment for choroidal neovascularization. As surgical treatment, the internal limiting membrane in areas surrounding the macular hole was detached after producing artificial posterior vitreous detachment, and a gas tamponade was performed. It was found during surgery that the extensibility of the retina in the margin of the MH was decreased in the three eyes as compared with a usual macular hole. Although the macular hole was successfully closed in all three cases post surgery, the layer structure of the central retina was poorly repaired in all three cases and choroidal neovascularization remained in one case. In all three cases, corrected visual acuity remained at 0.3–0.5 post surgery.ConclusionsOur findings showed poor improvement of visual acuity in all three cases post surgery, even if closure of the macular hole is achieved, thus suggesting that in cases of macular hole associated with tilted disc syndrome and inferior posterior staphyloma, the presence of macular dysfunction existing prior to the onset of macular hole affects visual prognosis.

Macular Telangiectasia type 2: multimodal assessment of retinal function and microstructure.

To assess the impact of neurodegenerative morphologic alterations due to macular telangiectasia type 2 (MacTel) on microperimetry (MP) and multifocal electroretinography (mfERG). Thirty-five eyes of 18 patients with MacTel were examined using spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), mfERG and MP. Software was used to match SD-OCT B-scans with the corresponding retinal sensitivity map and multifocal electroretinograms (mfERGs), thus enabling direct structure/function correlation. Loss of the ellipsoid zone (EZ) had the strongest negative association with retinal sensitivity (16.77 dB versus 4.58 dB, adj. p < 0.001) of all parameters examined, and a limited negative effect on mfERGs (0.32 SD versus -1.97 SD adj. p = 0.121). Ellipsoid zone (EZ) irregularity was associated with reduced MP values but preserved mfERGs. There was a significant association between areas of inner retinal hyporeflectivity and loss of MP sensitivity (adj. p < 0.001) but the reduction in sensitivity was less than in locations with EZ loss. Areas of mfERG abnormality showed similar sensitivity loss with either inner retinal hyporeflectivity or EZ loss (adj. p = 0.063). In areas with EZ loss alone, preservation of the external limiting membrane (ELM) was associated with higher MP values than in areas with additional ELM loss; the integrity of the ELM alone was not associated with changes either in MP or mfERG. Increased FAF was observed in 51% of eyes, mixed/reduced FAF in 40%, and no abnormality was detected in 9% of eyes. The data suggest both MP and mfERG to be useful non-invasive modalities for detecting localised macular dysfunction in MacTel. The findings suggest a different sensitivity of the two modalities to inner and outer retinal changes in macular function and are therefore complementary.

A Comparison Among Microperimetry, Standard Automated Perimetry and Spectral Domain Optical Coherence Tomography in the Evaluation of the Macula in Glaucoma Eyes with Hemifield Defects.

IntroductionTo evaluate the correlation between macular integrity assessment (MAIA) and standard automated perimetry (SAP) in detecting macular function damage in glaucoma and to explore the relationship between macular structure and functional damage by using spectral domain optical coherence tomography (SD-OCT).MethodsThis was a cross-sectional study. Seventy patients with glaucoma, with hemifield defects verified by Humphrey 24-2 examination, and 60 normal subjects underwent Humphrey 10-2 and MAIA expert 10-2 examinations. Patients with glaucoma with normal hemifields, as detected by SAP, were divided into a normal hemifield group and a visual field (VF) defect group. The difference in the retina and ganglion cell complex (GCC) thicknesses was analyzed between the abnormal and normal hemifields.ResultsAmong the 70 glaucoma eyes, the results of MAIA and SAP were consistent for 66 (66/70, 94.3%). The others showed SAP hemifield defects, while MAIA was normal (4/70, 5.7%). There was a good correlation of the mean sensitivity between MAIA and SAP (P < 0.001). There also was a good correlation between the mean threshold of MAIA and the mean deviation (MD) of SAP (P = 0.008, r = 0.507). Among the patients with glaucoma with a normal hemifield, MAIA showed abnormal results in 50 eyes (50/66, 75.8%), which was consistent with the changes in the inner retina and GCC thicknesses. Meanwhile, MAIA showed normal results; there were no significant differences between patients with glaucoma and the normal group in the thicknesses of the inner retina and GCC.ConclusionMAIA and SAP have good consistency in detecting macular dysfunction. MAIA can also identify abnormal VFs in the macular regions that may not be detected by SAP, which is consistent with the changes in the GCC thicknesses, suggesting that there may be central VF damage in patients with glaucoma that has not been previously identified.

Macular Morpho-Functional and Visual Pathways Functional Assessment in Patients with Spinocerebellar Type 1 Ataxia with or without Neurological Signs.

Spinocerebellar ataxia type 1 (SCA-ATXN1) is an autosomal dominant, neurodegenerative disease, caused by CAG repeat expansion in the ataxin-1 gene (ATXN1). In isolated reports of patients with neurological signs [symptomatic patients (SP)], macular abnormalities have been described. However, no reports exist about macular anomalies in SCA1 subjects carrying the ATXN1 mutation without neurological signs [not symptomatic carriers (NSC)]. Therefore, the main aim of our work was to evaluate whether the macular functional and morphological abnormalities could be detectable in SP, genetically confirmed and with neurological signs, as well as in SCA-ATXN1-NSC, harboring pathogenic CAG expansion in ATXN1. In addition, we investigated whether the macular involvement could be associated or not to an impairment of RGCs and of their fibers and of the neural conduction along the visual pathways. Herein, nine SCA-ATXN1 subjects (6 SP and 3 NSC) underwent the following examinations: visual acuity and chromatic test assessments, fundus oculi (FO) examination, macular and peripapillary retinal nerve fiber layer thickness (RNFL-T) analysis by Spectral domain-Optical Coherence Tomography (Sd-OCT) acquisition, multifocal electroretinogram (mfERG), pattern reversal electroretinogram (PERG) and visual evoked potentials (VEP) recordings. In four eyes of two SP, visual acuity reduction and chromatic abnormalities were observed; in three of them FO changes associated with macular thinning and outer retinal defects were also detected. In three NSC eyes, slight FO abnormalities were associated with qualitative macular morphological changes. By contrast, abnormal mfERG responses (exclusively from foveal and parafoveal areas) were detected in all SP and NSC (18 eyes). No abnormalities of PERG values, RNFL-T, and VEP responses were found, but in one SP, presenting abnormal papillo-macular bundle neural conduction. Results from our SCA-ATXN1 cohort suggest that a macular dysfunction, detectable by mfERG recordings, may occur in the overt disorder, and unexpectedly in the stage of the disease in which there is still an absence of neurological signs. In NSC, an exclusive dysfunction of preganglionic macular elements can be observed, and this is associated with both normal RGCs function and neural conduction along the visual pathways.

Localized Structural and Functional Deficits in a Nonhuman Primate Model of Outer Retinal Atrophy.

PurposeCell-based therapy development for geographic atrophy (GA) in age-related macular degeneration (AMD) is hampered by the paucity of models of localized photoreceptor and retinal pigment epithelium (RPE) degeneration. We aimed to characterize the structural and functional deficits in a laser-induced nonhuman primate model, including an analysis of the choroid.MethodsMacular laser photocoagulation was applied in four macaques. Fundus photography, optical coherence tomography (OCT), dye angiography, and OCT-angiography were conducted over 4.5 months, with histological correlation. Longitudinal changes in spatially resolved macular dysfunction were measured using multifocal electroretinography (MFERG).ResultsLesion features, depending on laser settings, included photoreceptor layer degeneration, inner retinal sparing, skip lesions, RPE elevation, and neovascularization. The intralesional choroid was degenerated. The normalized mean MFERG amplitude within lesions was consistently lower than control regions (0.94 ± 0.35 vs. 1.10 ± 0.27, P = 0.032 at month 1, 0.67 ± 0.22 vs. 0.83 ± 0.15, P = 0.0002 at month 2, and 0.97 ± 0.31 vs. 1.20 ± 0.21, P < 0.0001 at month 3.5). The intertest variation of mean MFERG amplitudes in rings 1 to 5 ranged from 13.0% to 26.0% in normal eyes.ConclusionsLaser application in this model caused localized outer retinal, RPE, and choriocapillaris loss. Localized dysfunction was apparent by MFERG in the first month after lesion induction. Correlative structure-function testing may be useful for research on the functional effects of stem cell–based therapy for GA. MFERG amplitude data should be interpreted in the context of relatively high intertest variability of the rings that correspond to the central macula. Sustained choroidal insufficiency may limit long-term subretinal graft viability in this model.

Correlation Between Choriocapillaris Density and Retinal Sensitivity in Age-Related Macular Degeneration.

PurposeThe purpose of this study was to investigate the relationship between perfusion of the choriocapillaris (CC) and retinal sensitivity in eyes with intermediate age-related macular degeneration (iAMD).MethodsThis prospective study included patients with iAMD and healthy controls. All enrolled subjects underwent optical coherence tomography angiography (OCT-A) in order to compute the percent perfused choriocapillaris area (PPCA). In patients with iAMD, microperimetry (MP) testing was performed in order to quantify: mean retinal sensitivity (MRS), over an area of 10 degrees; mean macular sensitivity (MMS), over the macular area scanned with OCT-A; and retinal sensitivity (RS) in each macular point.ResultsEighteen eyes of 13 patients were included in the analysis. In addition, 18 eyes of 12 healthy subjects were enrolled as controls. No statistically significant difference (P value > 0.2) was observed in age between patients (73.9 ± 2.0 years) and controls (70.1 ± 2.8 years). We observed significantly lower values of PPCA between patients with iAMD and healthy controls (42.0% ± 3.8% vs. 66.4% ± 3.0%; -β = 23.8%; P value < 0.001). Among iAMD eyes, higher values of PPCA were significantly associated with higher values of MRS (P value = 0.002) and MMS (P value = 0.013). Finally, higher values of RS in each macular point analyzed with MP were significantly (P value < 0.001) associated with higher values of PPCA computed in circular regions of interest (ROIs) centered in each analyzed MP point with radii of 0.5 degrees and 1.0 degree.ConclusionsUsing OCT-A, we demonstrated a significant association between CC impairment and macular dysfunction, quantified by MP, in iAMD eyes.Translational RelevanceOCT-A could be a useful tool for detecting CC alterations and to monitor disease progression.