Retinal Vessel Attenuation Research Articles

Genetic and phenotypic presentation of Usher syndrome - a case report

Usher syndrome is a genetic, clinically heterogeneous condition characterized by sensorineural hearing loss, progressive retinal degeneration, and vestibular dysfunction. There are three phenotypically recognizable types of Usher syndrome. Individuals with Usher syndrome type 1 have no vestibular function and profound sensorineural hearing loss. Individuals with Usher syndrome type 2 have normal vestibular function and mild-to-severe hearing loss with visual impairment that is presented later in life. People with Usher syndrome type III experience hearing and vision loss beginning later in life. In this case report, we are reporting a 7-year-old boy consulted for progressive hearing loss and bilateral vision impairment, and fundus exam revealed mild bilateral retinal vessel attenuation and bone spicule deposits in both eyes. A molecular genetic test done by next-generation sequencing identified a homozygous pathogenic variant in the CDH23 gene (NM_022124.5:c.2255del variant coordinate with amino acid change of p.(Gly752Valfs*13)), confirming the diagnosis of autosomal recessive Usher syndrome type ID (USH1D). The patient had a remarkable improvement with visual and optical aids. Genetic counseling, including reproductive counseling, was provided to the parents. Clinical evaluation, visual hearing tests, and genetic workup confirmed Usher syndrome, which is a rare but dangerous cause of hearing loss and visual impairment that needs to be thoroughly evaluated by a multi-disciplinary team approach.

Progressive retinal atrophy in Turkish Shepherd Dog; A case report

Progressive retinal atrophy (PRA) is described as an inherited degenerative disease of the retina that is common in dogs. The case was a 9-year-old female Turkish shepherd dog. It was presented to the Small Animal Hospital with complaints of polyuria and stranguria. After examination, the diagnosis was acute hepatitis. Medical treatment (ursofalk, milk thistle, prednisolone and N acetyl cystein) was given. The case lost vision after three days of treatment. The ophthalmological examinations were performed as included slit lamp, Schirmer's tear test, applanation tonometry, fluorescein staining and ultrasound. Ophthalmoscopic and fundoscopic examinations revealed hyperreflectivity and colour change in the tapetal region, marked attenuation of retinal vessels, depigmentation in the non-tapetal region, and optic disc atrophy with scalloped borders. Fundoscopic examination revealed retinal degeneration in both eyes. The aim of this case report is to diagnose PRA in Turkish shepherd dogs, to highlight its significance and to share the results with clinicians.

FDXR-Associated Oculopathy: Congenital Amaurosis and Early-Onset Severe Retinal Dystrophy as Common Presenting Features in a Chinese Population.

Variants in FDXR reportedly cause autosomal recessive auditory neuropathy and optic atrophy, expanding to retinal dystrophy. This study aimed to further clarify associated phenotypes. FDXR variants were selected from our in-house whole-exome sequencing dataset of 6397 families with different eye conditions. The clinical data of the identified patients were summarized. Biallelic pathogenic or likely pathogenic FDXR variants were identified in 11 unrelated patients, including 14 missense variants of which 10 were novel. Fundus observation showed complete optic disc pallor, silver wiring or severe attenuation of retinal vessels, and varying degrees of generalized retinal degeneration. Before the detection of FDXR variants, four patients were clinically diagnosed as congenital amaurosis due to the presence of nystagmus a few months after birth, while seven were diagnosed as early-onset severe retinal dystrophy due to the presence of nyctalopia and/or poor vision in early childhood. Biallelic FDXR variants are a frequent cause of congenital or early-onset severe retinal dystrophy, especially for patients with severe optic atrophy and retinal dystrophy in early childhood.

Retinal changes in patients with idiopathic inflammatory myopathies: A case-control study in the MyoCite cohort.

Retinal changes are the window to systemic vasculature. Therefore, we explored retinal changes in patients with Idiopathic inflammatory myopathies (IIM) as a surrogate for vascular health. Adult and Juvenile IIM patients (2017 ACR/EULAR criteria), visiting a tertiary care center in 2021 were enrolled for detailed ophthalmic examination in comparison with healthy controls (HC). Patients with conditions that precluded thorough posterior chamber examination were excluded. Scale variables are expressed as median (IQR). Multivariate analysis (binary logistic regression-BLR) was conducted, adjusting for age, gender, and comorbidities besides factors significant in univariate analysis. 43 patients with IIM [31 females; age 36 (23-45) years; disease duration 5.5 (2-12) months] were enrolled for participation. DM (44%) was the most common diagnosis. IIM patients exhibited frequent attenuation of retinal vessels (32.6 vs. 4.3%, p < 0.001), AV nicking (14 vs. 2.2%, p = 0.053), and vascular tortuosity (18.6 vs. 2.2%, p = 0.012), besides decreased visual acuity (53.5 vs. 10.9%, p<0.001) and immature cataracts (34.9 vs. 2.2%, p < 0.001). Attenuation of vessels [OR 10.9 (1.7-71), p = 0.004] emerged as significantly different from HC after adjusting for covariates in BLR. Notably, adults with IIM were more predisposed to retinal abnormalities [21 (57%) vs. 1 (16%), p = 0.068], especially attenuation of vessels [14(38%) vs. 0(0), p = 0.067] than jIIM. However, no difference was found in retinal features amongst the subtypes of adult IIM, nor did they correlate with MDAAT, MDI, or HAQ-DI. Retinal microvasculopathy and diminution of vision occur in nearly one-thirds to half of the patients with IIM. Microvasculopathy occurs across subtypes of IIM, and more so in adults, calling for further investigation as a surrogate for damage assessment and potentially even systemic vascular health.

An inherited night blindness in Wiltshire sheep.

Twelve cases of adult-onset blindness were identified in a flock of 130 polled Wiltshire sheep in New Zealand over a 3-year period. Affected sheep developed night blindness between 2 and 3 years of age, which progressed to complete blindness by 4 to 5 years of age. Fundic examination findings included progressive tapetal hyperreflectivity and attenuation of retinal blood vessels. Histologically, the retinas had a selective loss of rod photoreceptors with initial preservation of cone photoreceptors. Retinal degeneration was not accompanied by any other ocular or central nervous system abnormalities, and pedigree analysis suggested an inherited basis for the disease. Mating an affected Wiltshire ram to 2 affected Wiltshire ewes resulted in 6 progeny that all developed retinal degeneration by 2 years of age, while mating of the same affected ram to 6 unaffected ewes resulted in 8 unaffected progeny, consistent with autosomal recessive inheritance. Homozygosity mapping of 5 affected Wiltshire sheep and 1 unaffected Wiltshire sheep using an OvineSNP50 Genotyping BeadChip revealed an identical-by-descent region on chromosome 5, but none of the genes within this region were considered plausible candidate genes. Whole-genome sequencing of 2 affected sheep did not reveal any significant mutations in any of the genes associated with retinitis pigmentosa in humans or progressive retinal atrophy in dogs. Inherited progressive retinal degeneration affecting rod photoreceptors has not been previously reported in sheep, but this disease has several similarities to inherited retinal dystrophies in other species.

Computer-assisted retinal vessel diameter evaluation in Fabry disease.

Fabry disease retinal vascular involvement has been widely reported, with narrowing of the retinal arterioles, dilation and irregularity of the retinal veins, and exaggerated tortuosity of the retinal vessels. We evaluated retinal vessel diameter in Fabry disease, by means of a dedicated software, aiming to provide a quantitative marker of retinal vascular network abnormalities in Fabry disease patients. Observational case-control study evaluating different branches of vessels, peripapillary vessels (group A), temporal vascular arcades (group B), and second-order collaterals of the temporal arcades (group C). We obtained the vessel diameters values from eye fundus digital images of eight Fabry disease patients and eight age-sex matched controls, using a semiautomatic software. Mann-Whitney test was used to compare the Fabry disease group versus the control group. The difference between the average diameters of all the types of vessels considered were significantly smaller in Fabry disease patients compared to healthy controls, resulting in a decrease in size (mm) of 10.9% for group A, 7.8% for group B, and 7.4% for group C. The most evident difference between Fabry disease patients and controls was found in the largest vessels. A computer-assisted analysis of retinal vessel diameter in Fabry disease by means of dedicated software showed narrower retinal arteries in Fabry disease patients than in controls. Our data support the use of semiautomatic assessment of retinal vessel attenuation as an objective and reproducible method to evaluate retinal vascular alterations in Fabry disease, providing a clinical non-invasive tool for early diagnosis and disease monitoring.

Ciliopathy: Bardet-Biedl Syndrome.

Bardet-Biedl syndrome (BBS) is an autosomal recessive disease with a prevalence of about 1/125,000. The syndrome involves mixed rod-cone dystrophy (which becomes obvious by 6&#x00A0;years of age). About two thirds of patients have postaxial polydactyly, and sometimes syndactyly, brachydactyly, and/or clinodactyly may be present. Hypogonadism and renal involvement occur in about 40%, mental retardation in about 50%, and truncal obesity in about 70%; it is present early, along with insulin resistance, type 2 diabetes, dyslipidemia, and hypertension. Vision becomes markedly impaired by about age 30&#x00A0;years. The BBS is genetically heterogeneous entity with considerable phenotypic variability. Other associated problems include CNS-related ataxia, abnormal gait, and facial hypotonia, as well as anomalies such as high palate, hearing loss, and cardiac malformations. In males, there is oligospermia, leading to infertility. Around 50&#x2013;80% of BBS patients have renal malformations (like cyst, agenesis or scarring) and renal dysfunction leading to end-stage renal disease. There are no pigmentary changes before the age of 1&#x2013;2&#x00A0;years. Later, subtle pigmentary changes appear in the macula or peripapillary area. Several years later, pigments appear in the equatorial region, along with attenuation of retinal blood vessels and waxy pallor of the optic disc. Eventually, the macula may show atrophic changes (Figs. 33.1, 33.2 and 33.3). Electroretinography (ERG) shows involvement of rods and cones and is abnormal even before the fundus shows changes. A perimacular hyperfluorescent ring can be seen.

The Rapid-Onset Chorioretinopathy Phenotype of ABCA4 Disease

To characterize patients affected by a uniquely severe, rapid-onset chorioretinopathy (ROC) phenotype of ABCA4 disease. Comparative cohort study. Sixteen patients were selected from a large clinically diagnosed and genetically confirmed cohort (n= 300) of patients diagnosed with ABCA4 disease. Phenotypic characteristics were assessed on color fundus photographs, short-wavelength autofluorescence (488-nm), and near-infrared autofluorescence (NIR-AF, 787-nm) images. Subfoveal thickness measurements were obtained from enhanced-depth imaging OCT. Generalized retinal function was determined with full-field electroretinogram (ffERG) testing, and lipofuscin accumulation was assessed by quantitative autofluorescence (qAF). All patients exhibited advanced disease features, including pigment migration in the macula and retinal vessel attenuation at an early age, and reported a symptomatic onset, on average, at 7.4 years (average for ABCA4 disease is 21.9 years, P < 0.0001). Deterioration of the macula was observed to begin with an intense, homogeneous signal on short-wavelength autofluorescence, which corresponds to an attenuated NIR-AF signal and progresses to a patchy, coalescing pattern of chorioretinal atrophy within the subsequent decade. Measurement of choroidal thickness revealed a more rapid thinning of choriocapillaris with age of Sattler's layer compared with the rate in most other patients with ABCA4 disease (P < 0.001). Levels of qAF in the macula before atrophy were above both the 95% confidence intervals for healthy individuals and patients with Stargardt disease (STGD1) (>1000 qAF units). Severe attenuation of cone responses and notable decreases in rod responses were detected by ffERG. Sequencing of the ABCA4 gene revealed exclusively deleterious, null mutations, including stop codons; frameshift deletions; variants in canonical splice sites, which completely abolish splicing; and known deleterious missense alleles. The ROC phenotype is a unique classification of ABCA4 disease, which is caused by deleterious null biallelic ABCA4 mutations and is characterized by the rapid deterioration of retinal pigment epithelium and photoreceptor layers in the macula and significant choroidal thinning within the first 2 decades of life.

Clinical studies on progressive retinal atrophy in 31 dogs.

During a 2-year period, 31 cases of a hereditary retinal degeneration in dogs bred in India were found mainly suspected for progressive retinal atrophy (PRA) with typical history of initial nyctalopia followed by hemeralopia. Out of 31 PRA suspected dogs, 8 dogs (26%) were from the age group of 1-5 years, 15 (48%) 6-10 years and the rest (26%) 11-15 years. The most predominant breed was Spitz (18 dogs, 58%). Detailed ophthalmologic examinations included Schirmer's tear test, fluorescein stain, applanation tonometry, slit lamp biomicroscopy and ocular ultrasound in appropriate cases. Ophthalmoscopic and fundoscopic changes included hyperreflectivity and discoloration of the tapetal area, marked attenuation of retinal vessels, depigmentation in non-tapetal area and optic disc atrophy with scalloped borders. Electroretinograms (ERG) recorded in 13 PRA-affected cases revealed non-recordable extinguished (flatline) ERG responses. A reduction mainly of a- and b-wave amplitudes in the ERG indicated a generalized photoreceptor disease.

Arteriolar Diameters in Glaucomatous Eyes with Single-Hemifield Damage.

To examine the association between retinal arteriolar caliber and lumen, retinal sensitivity (RS), and retinal nerve fiber layer (RNFL) thickness in glaucomatous eyes with single-hemifield loss. We conducted a prospective, nonrandomized, case-control study of 20 eyes of 20 patients with glaucoma with visual field damage confined to a single hemifield. The control group was composed of 20 eyes of 20 normal subjects. For all the eyes, we performed optical coherence tomography to assess the RNFL and standard automated perimetry to evaluate RS. External and internal arteriolar diameters were assessed in vivo using scanning laser Doppler flowmetry. The RNFL was significantly thinner in glaucomatous eyes than in normal eyes (p < 0.001). In glaucomatous eyes, a positive correlation between sectorial RNFL thickness and the corresponding external and internal arteriolar diameters was found (r = 0.43, p = 0.05; r = 0.63, p = 0.003, respectively). The internal arteriolar diameter significantly correlated with RS in the corresponding abnormal hemifield (r = 0.44, p = 0.04). Compared with the normal hemifield, the internal arteriolar diameter, RNFL thickness, and RS were significantly reduced, whereas the external arteriolar diameter was unchanged in the abnormal hemifield. In glaucomatous eyes with single-hemifield damage, attenuation of retinal vessels was associated with a thinner RNFL and reduced RS. Moreover, a narrower lumen with increased wall-to-lumen ratio was found in the abnormal hemifield, supporting the hypothesis that vessel narrowing is likely secondary to a lower demand for blood flow in the glaucomatous areas of the retina.

Computer-Assisted Evaluation of Retinal Vessel Diameter in Retinitis Pigmentosa

Purpose: The evaluation of retinal vessel attenuation is very subjective and not sufficiently reliable in patients with retinitis pigmentosa (RP). We tested semiautomatic software capable of obtaining real-time measurements of vessel diameter. Methods: Retinal vessel diameter was calculated in 25 RP subjects and in 20 healthy controls. The Mann-Whitney test was used to compare the average values of RP patients with those of controls and subgroups of RP patients with different clinical features. Results: The retinal vessel diameter was significantly smaller in RP patients than in controls (p < 0.001). In particular, vessel diameters were smaller in older subjects, in patients with worse ERG responses, and in patients with more severe visual field loss. Conclusions: Computer-assisted analysis of retinal fundus pictures may be helpful in the diagnosis of RP and in monitoring disease progression.

Chloroquine retinopathy: pattern of presentation in Ibadan, Sub-Sahara Africa.

BackgroundSelf-medication with chloroquine is common in Ibadan, Sub-Sahara Africa. Retinopathy from chloroquine is not uncommon. The aim was to determine the pattern of presentation.MethodologyCases of Chloroquine retinopathy seen at the Retina and Vitreous Unit of the University College Hospital, Ibadan between 2008 and 2014 were reviewed. Information on age, sex, duration of chloroquine use, and visual loss were retrieved. Visual acuity at presentation, anterior, and posterior segment findings were documented. The results were analyzed using proportions and percentages.ResultsFourteen cases were seen during the study period. Mean age was 50.7 years. Male to female ratio was 3.5 : 1. Average duration of visual loss before presentation was 2.7 years. Average duration of self-medication with chloroquine was 5.3 years. Presenting visual acuity showed 2(14%) cases of bilateral blindness(VA<3/60 in both eyes); 5(35.7%) cases of uniocular blindness; three cases of bilateral low vision(VA worse than 6/18 but better than 3/60). Anterior segment examination showed abnormal sluggish pupillary reaction in those with severe affectation. Dilated fundoscopy showed features ranging from mild macular pigmentary changes and bulls eye maculopathy to overt extensive retinal degeneration involving the posterior pole, attenuation of retinal vessels, optic atrophy, and beaten bronze appearance of atrophic maculopathy.ConclusionChloroquine retinopathy is not uncommon in Ibadan, Sub-Sahara Africa. Bulls eye maculopathy, extensive retinal, and macular degeneration with optic atrophy are the main presentations. Public health education is imperative.

Whole-exome sequencing reveals a novel CHM gene mutation in a family with choroideremia initially diagnosed as retinitis pigmentosa.

BackgroundGenomic mutations in about 200 genes are associated with hereditary retinal diseases. In this study, we screened for the disease-causing gene mutation in a family with X-linked retinal degenerative disease.MethodsPedigree data were collected and genomic DNA was isolated from peripheral blood of family members, who also underwent comprehensive ophthalmic examination including visual acuity, slit-lamp examination, fundus examination and visual field testing at Qilu Hospital of Shandong University. Whole-exome genomic sequencing was used to screen for gene mutations in the male proband. Sanger sequencing was used to confirm the mutation revealed in this family.ResultsTwo affected males underwent ophthalmic examination; retinitis pigmentosa (RP) was diagnosed on the basis of night blindness beginning at an early age, decreasing visual acuity, progressive loss of peripheral vision, attenuation of retinal vessels and pigment disturbance on fundus examination. However, whole-exome sequencing revealed no mutation in RP-associated genes. Instead, we identified a novel hemizygous c.1475_1476insCA mutation in the choroideremia-associated gene (CHM). The mutation was confirmed by Sanger sequencing and further excluded from the possibility as a rare polymorphism. From the genetic data and clinical findings, the diagnosis was corrected to choroideremia (CHM). Further molecular genetic analysis suggested that this novel CHM mutation caused a frame shift (p.Leu492PhefsX7) and encoded a truncated nonfunctional Rab escort protein 1 (REP-1), which caused CHM in this family. Finally, sequencing data for a pregnant female member confirmed that she did not carry the mutation and thus was carrying a healthy infant.ConclusionWe report a novel CHM mutation, c.1475_1476insCA, identified by whole-exome sequencing in a family with X-linked CHM initially diagnosed as RP. Our findings emphasize the value of a diagnostic approach that associates genetic and ophthalmologic data to facilitate the proper clinical diagnosis of rare hereditary retinal diseases such as CHM.

Association of retinal vessel attenuation with visual function in eyes with retinitis pigmentosa.

PurposeTo investigate the association between visual changes and retinal vessel attenuation in patients with retinitis pigmentosa (RP).DesignA retrospective, longitudinal, observational cohort study.MethodsWe analyzed 45 eyes from 45 subjects who were followed-up for ≥3 years at our clinic. Using the computer-based Interactive Vessel Analysis program, central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) were determined. Age- and sex-matched controls from normal subjects were selected from our archived fundus photograph library. Visual acuity, visual field area (Goldmann perimetry, V4e white test light), mean deviation (Humphrey perimetry, central 10-2 program), and central macular thickness (optical coherence tomography) were analyzed for correlations with CRAE and CRVE.ResultsBoth CRAE and CRVE were significantly decreased in RP eyes (94.9±13.5 μm and 155.6±20.0 μm, respectively) compared with control eyes (138.1±14.7 μm and 215.0±20.4 μm, respectively, both P<0.001). After 3 years of follow-up, visual field area was associated with both CRAE (r=0.584, P<0.01) and CRVE (r=0.500, P=0.008). A significant association was also observed between mean deviation and CRAE (r=0.298, P=0.047). In eyes with RP, a narrower vessel caliber at baseline was associated with a larger decline in visual acuity over the 3-year follow-up interval (CRAE: r=−0.344, P=0.021; CRVE: r=−0.314, P=0.035).ConclusionRetinal vessel caliber is associated with some visual functions in patients with RP.

Late recurrence of retinopathy of prematurity after treatment with both intravitreal bevacizumab and laser

An infant of 36 weeks' postmenstrual age (PMA) and 25weeks' gestation received bilateral intravitreal bevacizumab injections for type 1 retinopathy of prematurity. He underwent laser photocoagulation in both eyes 5 days later, confluent except for 1 clock hour obscured by hemorrhage in the left eye. Despite initial regression, neovascularization in both vascularized and lasered retina with plus disease recurred, requiring repeat laser bilaterally at 51 weeks' PMA and vitrectomy in the left eye at 54 weeks' PMA. Whereas late recurrence is thought to occur rarely after laser treatment, infants who have received both bevacizumab injections and laser may still require long-term surveillance for recurrence. In this case, fundus photography proved valuable for appreciating recurrent plus disease because the initial treatments had resulted in marked retinal vessel attenuation.

Clinical and Electroretinographic Findings of Progressive Retinal Atrophy in Miniature Schnauzer Dogs of South Korea

ABSTRACTThe purpose of the study was to describe the clinical and electroretinographic features of clinical cases of progressive retinal atrophy (PRA) in miniature schnauzer (MS) of South Korea. Sixty-six MS (14 normal and 52 affected) were included. All animals underwent routine ocular examinations. Electroretinogram (ERG) was recorded in the 14 normal and 15 affected dogs. For normal dogs, the mean age ± SD was 4.1 ± 2.4 years (1 to 9 years), and there were no ocular abnormalities on the basis of ocular examinations and ERG results. For the PRA-affected dogs, it was shown that the mean age ± SD was 4.3 ± 1.1 years (2 to 7 years), and 44 dogs (84.6%) were 3 to 5 years old. Most of the PRA-affected dogs had abnormal menace responses (98.1%) and pupillary light reflexes (PLRs, 88.5%); some dogs showed normal menace response (1.9%) and PLRs (11.5%). Ophthalmoscopic abnormalities in the affected group included one or more of the following changes: hyperreflectivity and discoloration of the tapetal area, attenuation of retinal vessels, depigmentation in non-tapetal area and optic disc atrophy. ERG in the affected dogs showed non-recordable responses in all cases tested with clinical signs of PRA. The present study showed that PRA in MS was mainly observed between the age of 3 to 5 years. ERG revealed abnormal rod and cone responses in affected dogs at the ages studied.

Bilateral macular coloboma in a patient with retinitis pigmentosa like changes

AbstractPurpose To report a case with bilateral macular coloboma and RP (retinitis pigmentosa) like changes.Methods A 46‐year‐old female presented with macular coloboma in both eyes. There was a history of strabismic amblyopia in her right eye but no other contributory medical or family history.Best corrected Snellen visual acuity (BCVA) was measured and full ophthalmic examination was performed. Visual field testing, optical coherence tomography (OCT) and international‐standard electrophysiological (ISCEV) evaluation, including pattern and full‐field electroretinography (PERG and FFERG), were also performed.Results BCVA was hand movements in the right eye and 0.5 in her left eye. Fundoscopy revealed an oval sharply‐ demarcated defect at the macula with bare sclera at its base and pigment clumping, mainly in the right eye, resembling macular coloboma. There were also severe retinal vessel attenuation and scattered retinal pigmentary changes, occasionally resembling bone spicule RPE changes, in the retinal periphery in both eyes. Optic discs were pale bilaterally. Visual field testing demonstrated bilateral scotomas. OCT revealed a crater‐like depression at the macula with atrophic neurosensory retina and absence of retinal pigment epithelium (RPE) and choroid, more extensive in her right eye, where scleral excavation was also documented. Pattern ERG as an indication of macular function was extinguished in the right eye and severely affected in her left eye. Full field ERG was extinguished bilaterally for both scotopic and photopic responses.Conclusion Bilateral macular coloboma associated with RP like changes, an abnormal electroretinography and no relevant family history, may be indicative of a developmental retinal abnormality.

Quantitative Analysis of Retinal Vessel Attenuation in Eyes with Retinitis Pigmentosa

Retinal vessel attenuation is a key finding in the diagnosis of retinitis pigmentosa (RP), but there have been no studies to determine whether quantitative measurement of this retinal sign is useful. We aimed to investigate retinal vessel caliber and its relationship with the severity of RP. This is a cross-sectional study based on 74 patients (145 eyes) with RP who had visual field assessment with Goldmann permeter and good-quality retinal images for vessel size measurements identified by retrospective medial chart review (1973-2007) in the electrophysiology clinic of a tertiary eye hospital in Australia. Retinal vessel calibers were measured using a computer-based program as the central retinal artery and vein equivalent (CRAE and CRVE). Goldmann visual field area for III4e white test light was measured quantitatively using ImageJ software as a clinical parameter to indicate the severity of RP. We used the generalized estimating equation models to estimate the difference in retina vessel calibers accounting for correlation between right and left eyes. Mean CRAE and CRVE were significantly narrower in persons with smaller visual field area. For each 100 cm2 decrease in visual field area, CRAE and CRVE decreased by -15.2 μm (95% confidence interval -20.7, -9.78) and -26.8 μm (-35.1, -18.5), respectively (both P<0.001). In RP patients, the severity of visual field loss is correlated with retinal vessel attenuation. Quantitative retinal vessel caliber measurement may be a useful additional clinical marker for monitoring progression of RP or potential treatment response.

Mutations in C8orf37, Encoding a Ciliary Protein, are Associated with Autosomal-Recessive Retinal Dystrophies with Early Macular Involvement

Cone-rod dystrophy (CRD) and retinitis pigmentosa (RP) are clinically and genetically overlapping heterogeneous retinal dystrophies. By using homozygosity mapping in an individual with autosomal-recessive (ar) RP from a consanguineous family, we identified three sizeable homozygous regions, together encompassing 46 Mb. Next-generation sequencing of all exons, flanking intron sequences, microRNAs, and other highly conserved genomic elements in these three regions revealed a homozygous nonsense mutation (c.497T>A [p.Leu166(∗)]) in C8orf37, located on chromosome 8q22.1. This mutation was not present in 150 ethnically matched control individuals, single-nucleotide polymorphism databases, or the 1000 Genomes database. Immunohistochemical studies revealed C8orf37 localization at the base of the primary cilium of human retinal pigment epithelium cells and at the base of connecting cilia of mouse photoreceptors. C8orf37 sequence analysis of individuals who had retinal dystrophy and carried conspicuously large homozygous regions encompassing C8orf37 revealed a homozygous splice-site mutation (c.156-2A>G) in two siblings of a consanguineous family and homozygous missense mutations (c.529C>T [p.Arg177Trp]; c.545A>G [p.Gln182Arg]) in siblings of two other consanguineous families. The missense mutations affect highly conserved amino acids, and in silico analyses predicted that both variants are probably pathogenic. Clinical assessment revealed CRD in four individuals and RP with early macular involvement in two individuals. The two CRD siblings with the c.156-2A>G mutation also showed unilateral postaxial polydactyly. These results underline the importance of disrupted ciliary processes in the pathogenesis of retinal dystrophies.

Retinal Vessel Caliber and Myopic Retinopathy: The Blue Mountains Eye Study

Purpose: To evaluate changes in the retinal vasculature in eyes with myopic retinopathy.Methods: Population-based, cross-sectional study. Emmetropic and myopic participants from the Blue Mountains Eye Study baseline survey were included in this study. Myopia was defined as a refractive error of less than −1.00 diopter. Myopic retinopathy was defined if either staphyloma, lacquer crack, Fuchs’ spot or chorioretinal atrophy were present in myopic eyes. Retinal vascular caliber was measured from fundus photographs using standardized methods. The association of retinal vascular caliber with myopic retinopathy was assessed using generalized estimating equation models.Results: A total of 2598 eyes of 1409 subjects were selected from 3654 baseline participants, with 2076 emmetropic eyes (normal controls), 486 myopic eyes without myopic retinopathy (myopic controls) and 36 myopic eyes with myopic retinopathy (cases). After adjusting for age, gender, height, body mass index and blood pressure, eyes with myopic retinopathy had significantly narrower mean arteriolar (166.6μm) and venular caliber (213.3μm), compared to normal (188.1μm and 226.9μm, respectively) or myopic control eyes (190.4μm and 227.0μm, respectively) (all P < 0.001). These retinal vessel caliber differences between myopic retinopathy and the two control groups remained significant after additional adjustment for refraction (all P < 0.001).Conclusions: Our findings suggest that myopic retinopathy is associated with attenuation of retinal vessels.