Search

This report cases of two patients who presented with a new paracentral scotoma following SARS-CoV-2 infection. Patient 1 is a 37-year-old Caucasian female in week 14 of an uncomplicated pregnancy presented with a 1-day history of abrupt onset, faintly colourful, left eye paracentral scotoma. This was 35 days following the onset of a febrile illness with cough and anosmia. SARS-CoV-2 nasopharyngeal swab was not performed during the infection, but subsequently positive serology (IgG) has been confirmed. Past medical history included acephalgic visual migraine aura and right toxoplasma chorioretinitis. Examination showed normal visual acuity, no uveitis and fundoscopy was normal in the left eye. OCT changes correlated with the location of the scotoma. A focal area of hyper-reflective change in the inner and outer plexiform layers with inner nuclear layer volume loss was seen consistent with paracentral acute middle maculopathy (PAMM). Bloods were normal, including ESR, CRP, lipids, glucose, ANA and anti-phospholipid antibodies. An electrocardiogram and carotid Doppler ultrasound were normal. Patient 2 is a 32-year-old Caucasian male presented with a 4-day history of abrupt onset, faintly colourful, right eye paracentral scotoma. This was 16 days following the onset of nasopharyngeal swab confirmed COVID-19. Past medical history included acephalgic visual migraine aura. Examination showed normal visual acuity, no uveitis and fundoscopy was normal. Changes on infrared reflectance (white arrow) and OCT correlated with the location of the scotomaA focal area of faint outer plexiform layer hyper-reflective change and disruption of the interdigitation zone were seen consistent with acute macular neuroretinopathy. These patients developed PAMM and AMN soon after confirmed SARS-CoV-2 infection and possibly represent postinfectious complications.

BackgroundIn chronic central serous chorioretinopathy (CSCR), fluid accumulates in the subretinal space. CSCR is a common visually disabling condition that develops in individuals up to 60 years of age, and there is no definitive treatment. Previous research suggests the mineralocorticoid receptor antagonist, eplerenone, is effective for treating CSCR; however, this drug is not licensed for the treatment of patients with CSCR. We aimed to evaluate whether eplerenone was superior to placebo in terms of improving visual acuity in patients with chronic CSCR.MethodsThis randomised, double-blind, parallel-group, multicentre placebo-controlled trial was done at 22 hospitals in the UK. Participants were eligible if they were aged 18–60 years and had had treatment-naive CSCR for 4 months or more. Patients were randomly assigned (1:1) to either the eplerenone or the placebo group by a trial statistician through a password-protected system online. Allocation was stratified by best-corrected visual acuity (BCVA) and hospital. Patients were given either oral eplerenone (25 mg/day for 1 week, increasing to 50 mg/day for up to 12 months) plus usual care or placebo plus usual care for up to 12 months. All participants, care teams, outcome assessors, pharmacists, and members of the trial management group were masked to the treatment allocation. The primary outcome was BCVA, measured as letters read, at 12 months. All outcomes apart from safety were analysed on a modified intention-to-treat basis (participants who withdrew consent without contributing a post-randomisation BCVA measurement were excluded from the primary analysis population and from most secondary analysis populations). The trial is registered with ISRCTN, ISRCTN92746680, and is completed.FindingsBetween Jan 11, 2017, and Feb 22, 2018, we enrolled and randomly assigned 114 patients to receive either eplerenone (n=57) or placebo (n=57). Three participants in the placebo group withdrew consent without contributing a post-randomisation BCVA measurement and were excluded from the primary outcome analysis population. All patients from the eplerenone group and 54 patients from the placebo group were included in the primary outcome. Modelled mean BCVA at 12 months was 79·5 letters (SD 4·5) in the placebo group and 80·4 letters (4·6) in the eplerenone group, with an adjusted estimated mean difference of 1·73 letters (95% CI −1·12 to 4·57; p=0·24) at 12 months. Hyperkalaemia occurred in eight (14%) patients in each group. No serious adverse events were reported in the eplerenone group and three unrelated serious adverse events were reported in the placebo group (myocardial infarction [anticipated], diverticulitis [unanticipated], and metabolic surgery [unanticipated]).InterpretationEplerenone was not superior to placebo for improving BCVA in people with chronic CSCR after 12 months of treatment. Ophthalmologists who currently prescribe eplerenone for CSCR should discontinue this practice.FundingEfficacy and Mechanism Evaluation Programme, and National Institute for Health Research and Social Care.

Use of anti-vascular endothelial growth factor (VEGF) therapies was introduced for the treatment of ocular disorders in 2005. In the UK, the current licensed and NICE approved indications are for the treatment of neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DMO), macular oedema secondary to a retinal vein occlusion (RVO) and choroidal neovascularization in pathological myopia. These diagnoses alone account for two-thirds of the main causes of legally registrable visual impairment and blindness. Ranibizumab (Lucentis®; Genentech/Novartis), a drug specifically designed for intraocular use, is the primary licensed medication. Controversially however, clinicians have been using an unlicensed cheaper drug, bevacizumab (Avastin®; Genentech/Roche), originally designed for systemic administration, with a similar mode of action and shown to have a similar efficacy. However, there are fears of greater side effects with bevacizumab though studies have not been sufficiently powered to show statistical difference. In the current global economic climate, anti-VEGF treatment places huge financial and logistical pressure on already strained health care systems. Bevacizumab is considerably more cost effective than ranibizumab, and thus using bevacizumab would widen access to treatment particularly in developing countries. This licensing issue also places clinicians in a difficult medico-legal position especially in Europe, where doctors are duty bound to use a licensed drug for a particular indication if this is available. As the indications of anti-VEGF therapies expand and the cost of health care provision becomes more expensive, the controversies surrounding their use will inevitably become more important.

Bilateral optic neuropathy in Dar es Salaam is now considered endemic and is estimated to affect 0.3-2.4% of young adults. The condition is characterized by a subacute bilateral loss of central vision of unknown aetiology. Findings of spectral domain optical coherence tomography have not previously been reported for these patients. All patients diagnosed with endemic optic neuropathy over a 2-year period at the Muhimbili National Hospital underwent spectral domain optical coherence tomography macular imaging. Scans were graded qualitatively for severity of retinal nerve fibre layer loss as well as the presence of microcystic macular changes, which have not previously been described in this condition. Of the 128 patients included (54.7% male; median age 20 years), severe retinal nerve fibre layer loss was found in 185 eyes (74.0%). There was full concordance in retinal nerve fibre layer thickness between the two eyes in 113 (91.1%) patients. Microcystic macular spaces were found in 16 (12.5%) patients and were bilateral in nine (7.0%) individuals. These changes were typically more prominent in the nasal than the temporal macula, predominantly involving the inner nuclear layer, and often occurred in an annular configuration that was evident on en face infra-red imaging, though not discernible on colour fundus photography or clinically. All patients with microcystic macular changes had severe thinning of the retinal nerve fibre layer (P = 0.02). Four patients in whom cystic spaces were demonstrated had sequential scans, and there was no detectable alteration in the configuration of these changes over a period of up to 16 months. This is the first study to document optical coherence tomography findings in endemic optic neuropathy. We have observed symmetrical severe loss of the caeco-central projection (papillomacular bundle) with otherwise well-preserved macular architecture. Also, we have observed microcystic retinal changes in a significant proportion of patients, which were associated with severe retinal nerve fibre layer loss. Similar changes have recently been reported from optical coherence tomography images of patients with multiple sclerosis, relapsing isolated optic neuritis, dominant optic atrophy, Leber's hereditary optic neuropathy and a patient with a chronic compressive optic neuropathy, supporting the hypothesis that this may be a non-specific phenomenon secondary to ganglion cell death. The correspondence of the changes to an annulus discernible on infra-red en face imaging, but not using other conventional retinal imaging techniques highlights the potential usefulness of this modality.

Purpose To establish the prevalence and heritability of cilioretinal arteries (CRAs), tilted discs (TDs) and situs inversus (SI). Methods Fundus photos from the Twins UK Adult Twin registry twin database were analyzed: 1812 individuals, 526 complete monozygotic (MZ) twin pairs and 336 complete dizygotic (DZ) pairs. Images were assessed non-stereoscopically on a computer screen by the same ophthalmologist for presence of CRAs, TDs or SI. Prevalence figures, probandwise concordances and heritabilities were calculated. Results Prevalence of a CRA in subjects’ right eyes was 28.6% (26.5–30.8). Prevalence of subjects with a CRA in at least one eye was 45.0% (42.6–47.5), with a TD in at least one eye was 1.2% (0.8–1.9), and with SI at least one eye was 0.5% (0.3–1.0). There was no association between birth weight and presence of CRA. Concordance for CRA in at least one eye (MZ twins) was 60% (95% CI 55–64), and (DZ) was 45% (95% CI 39–51). Heritability for CRAs in at least one eye was 49.4% (95% CI 38.1–59.7) and for both eyes was 32.9% (95% CI 10.4–53.3). We were unable to calculate meaningful heritabilities or concordances for TDs and situs SI, due to insufficient numbers. Conclusions The presence of CRAs appears to be moderately heritable, with greater variance explained by individual environmental factors or even stochastic events. They were not associated with low birth weight. Future genetic research and studies of birth/lifecourse cohorts may offer further insights into the etiology of congenital papillovascular abnormalities. Electronic supplementary material The online version of this article (10.1007/s00417-017-3859-7) contains supplementary material, which is available to authorized users.

Foveal hypoplasia and optic nerve misrouting are developmental defects of the visual pathway and only co-occur in connection with albinism; to date, they have only been associated with defects in the melanin-biosynthesis pathway. Here, we report that these defects can occur independently of albinism in people with recessive mutations in the putative glutamine transporter gene SLC38A8. Nine different mutations were identified in seven Asian and European families. Using morpholino-mediated ablation of Slc38a8 in medaka fish, we confirmed that pigmentation is unaffected by loss of SLC38A8. Furthermore, by undertaking an association study with SNPs at the SLC38A8 locus, we showed that common variants within this gene modestly affect foveal thickness in the general population. This study reveals a melanin-independent component underpinning the development of the visual pathway that requires a functional role for SLC38A8.

Leber congenital amaurosis (LCA) is a blinding retinal disease that presents within the first year after birth. Using exome sequencing, we identified mutations in the nicotinamide adenine dinucleotide (NAD) synthase gene NMNAT1 encoding nicotinamide mononucleotide adenylyltransferase 1 in eight families with LCA, including the family in which LCA was originally linked to the LCA9 locus. Notably, all individuals with NMNAT1 mutations also have macular colobomas, which are severe degenerative entities of the central retina (fovea) devoid of tissue and photoreceptors. Functional assays of the proteins encoded by the mutant alleles identified in our study showed that the mutations reduce the enzymatic activity of NMNAT1 in NAD biosynthesis and affect protein folding. Of note, recent characterization of the slow Wallerian degeneration (Wlds) mouse model, in which prolonged axonal survival after injury is observed, identified NMNAT1 as a neuroprotective protein when ectopically expressed. Our findings identify a new disease mechanism underlying LCA and provide the first link between endogenous NMNAT1 dysfunction and a human nervous system disorder.

The atonal homolog 7 (ATOH7) gene encodes a transcription factor involved in determining the fate of retinal progenitor cells and is particularly required for optic nerve and ganglion cell development. Using a combination of autozygosity mapping and next generation sequencing, we have identified homozygous mutations in this gene, p.E49V and p.P18RfsX69, in two consanguineous families diagnosed with multiple ocular developmental defects, including severe vitreoretinal dysplasia, optic nerve hypoplasia, persistent fetal vasculature, microphthalmia, congenital cataracts, microcornea, corneal opacity and nystagmus. Most of these clinical features overlap with defects in the Norrin/beta-catenin signalling pathway that is characterized by dysgenesis of the retinal and hyaloid vasculature. Our findings document Mendelian mutations within ATOH7 and imply a role for this molecule in the development of structures at the front as well as the back of the eye. This work also provides further insights into the function of ATOH7, especially its importance in retinal vascular development and hyaloid regression.

Anterior segment dysgenesis describes a group of heterogeneous developmental disorders that affect the anterior chamber of the eye and are associated with an increased risk of glaucoma. Here, we report homozygous mutations in peroxidasin (PXDN) in two consanguineous Pakistani families with congenital cataract-microcornea with mild to moderate corneal opacity and in a consanguineous Cambodian family with developmental glaucoma and severe corneal opacification. These results highlight the diverse ocular phenotypes caused by PXDN mutations, which are likely due to differences in genetic background and environmental factors. Peroxidasin is an extracellular matrix-associated protein with peroxidase catalytic activity, and we confirmed localization of the protein to the cornea and lens epithelial layers. Our findings imply that peroxidasin is essential for normal development of the anterior chamber of the eye, where it may have a structural role in supporting cornea and lens architecture as well as an enzymatic role as an antioxidant enzyme in protecting the lens, trabecular meshwork, and cornea against oxidative damage.

Background: Retinal pigment epithelial detachment (PED) is a recognised associated finding in central serous chorioretinopathy (CSC). We report our experience in treating patients using photodynamic therapy (PDT) in a variant of chronic CSC that presents with only an isolated PED. We present long-term follow-up data and novel observations on the pattern of retinal pigment epithelium (RPE) changes seen after treatment. Methods: Retrospective case series. Results and Discussion: CSC with subfoveal PED can be associated with a poor visual prognosis especially when the PED becomes chronic. PDT has been used to treat typical CSC with good outcomes. Three eyes in 3 patients were successfully treated with PDT, using the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy protocol. However, marked RPE disturbance was observed after treatment directly overlying the areas of brisk choroidal hyperpermeability.

OBJECTIVE: We aimed to quantify socio-economic and ethnic inequalities in diabetes retinal screening. METHODS: Data were analysed for the retinal screening programme for three South London boroughs for the 18-month period to February 2009. Sight-threatening diabetic retinopathy (STDR) was defined as the occurrence of diabetic maculopathy, severe non-proliferative or proliferative diabetic retinopathy. Odds ratios were adjusted for sex, age group, duration and type of diabetes, self-reported ethnicity and deprivation quintile by participant postal code. RESULTS: There were 76 351 records obtained but, after excluding duplicate and ineligible records, data were analysed for 59 495 records from 31 484 subjects. There were 7026 (22%) subjects called for appointments who were not screened in the period, with 24 458 (78%) having one or more screening episodes. Non-attendance for screening was highest in young adults aged 18-34 years (32%) and in those aged 85 years or greater (28%). In the most deprived quintile, non-attendance was 23% compared with 21% in the least deprived quintile [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.16-1.61, P < 0.001]. There were 2819 (11.5%) participants with STDR, including 10.8% in the least deprived quintile and 12.2% in the most deprived quintile (OR 1.10, 95% CI 0.95-1.16, P = 0.196). Compared with white Europeans (9.4%), STDR was higher in Africans (15.2%) and African Caribbeans (14.7%), resulting from a higher frequency of diabetic maculopathy. CONCLUSION: Socio-economic inequality in diabetes retinal screening may be smaller than reported in earlier studies. This study suggested an increased frequency of diabetic maculopathy among participants of African origins.

Contains fulltext : 53618.pdf (Publisher’s version ) (Closed access) Leber congenital amaurosis (LCA) causes blindness or severe visual impairment at or within a few months of birth. Here we show, using homozygosity mapping, that the LCA5 gene on chromosome 6q14, which encodes the previously unknown ciliary protein lebercilin, is associated with this disease. We detected homozygous nonsense and frameshift mutations in LCA5 in five families affected with LCA. In a sixth family, the LCA5 transcript was completely absent. LCA5 is expressed widely throughout development, although the phenotype in affected individuals is limited to the eye. Lebercilin localizes to the connecting cilia of photoreceptors and to the microtubules, centrioles and primary cilia of cultured mammalian cells. Using tandem affinity purification, we identified 24 proteins that link lebercilin to centrosomal and ciliary functions. Members of this interactome represent candidate genes for LCA and other ciliopathies. Our findings emphasize the emerging role of disrupted ciliary processes in the molecular pathogenesis of LCA.

Individuals born of consanguineous union have segments of their genomes that are homozygous as a result of inheriting identical ancestral genomic segments through both parents. One consequence of this is an increased incidence of recessive disease within these sibships. Theoretical calculations predict that 6% (1/16) of the genome of a child of first cousins will be homozygous and that the average homozygous segment will be 20 cM in size. We assessed whether these predictions held true in populations that have preferred consanguineous marriage for many generations. We found that in individuals with a recessive disease whose parents were first cousins, on average, 11% of their genomes were homozygous (n = 38; range 5%-20%), with each individual bearing 20 homozygous segments exceeding 3 cM (n = 38; range of number of homozygous segments 7-32), and that the size of the homozygous segment associated with recessive disease was 26 cM (n = 100; range 5-70 cM). These data imply that prolonged parental inbreeding has led to a background level of homozygosity increased approximately 5% over and above that predicted by simple models of consanguinity. This has important clinical and research implications.

Purpose To describe the clinical features in a series of patients with poststreptococcal uveitis and to review literature on the pathophysiology and management. Design Retrospective and descriptive case series. Participants Ten consecutive cases of poststreptococcal syndrome uveitis diagnosed between 1996 and 2003. Methods Review of patient case notes. Main Outcome Measures Age, laterality, clinical features, and anti-streptococcal lysin O titers. Results Ten consecutive cases of poststreptococcal syndrome uveitis were identified. All our cases had bilateral nongranulomatous inflammation and raised anti-streptococcal lysin O titers. Collating data from previous reports and this series showed that 96% of the patients were below 40 years of age, and 87.5% had evidence of previous streptococcal infection. One third of the patients had posterior segment involvement. In our patients, this was in the form of vitritis, focal retinitis, optic disc swelling, and multifocal choroiditis. Conclusions Poststreptococcal syndrome uveitis should be considered in the etiology of acute bilateral nongranulomatous uveitis in children and young patients.

The phrase anterior segment dysgenesis (ASD), also sometimes known as anterior segment ocular or mesenchymal dysgenesis (ASOD or ASMD, OMIM #107250), was first used in 1981 by Hittner and colleagues to describe a range of developmental defects in structures at the front of the eye.1 These defects are thought to result from abnormal migration or differentiation of the neural crest derived mesenchymal cells that give rise to the cornea, iris, and other components of the anterior chamber during eye development.2,3 Conditions falling within the ASD spectrum include aniridia, posterior embryotoxon, Axenfeld’s anomaly, Reiger’s anomaly/syndrome, Peters’ anomaly, and iridogoniodysgenesis. Aniridia (OMIM #106210) ranges from almost complete absence of the iris, through enlargement and irregularity of the pupil mimicking a coloboma, to small slit-like defects in the anterior layer visible only with a slit lamp. In Axenfeld’s anomaly (OMIM #109120), the Schwalbe’s line is prominent and centrally displaced (posterior embryotoxon) with peripheral iris strands fused to it. Eye signs in Rieger’s anomaly (OMIM #109120) patients may include malformations of the anterior chamber angle and aqueous drainage structures (iridogoniodysgenesis), microcornea, iris hypoplasia, eccentric pupil (corectopia), iris tears (polycoria), and iridocorneal tissue adhesions traversing the anterior chamber angle.4,5 In Reiger’s syndrome (OMIM #180500), patients have ASD in association with underdeveloped or misshapen teeth (hypodontia) and may also have hearing loss, heart defects and skeletal abnormalities. Peters’ anomaly (OMIM #604229) consists of a central corneal leucoma, absence of the posterior corneal stroma and Descemet membrane, and varying degrees of iris and lenticular attachment to the posterior cornea. All of these conditions carry with them an increased risk of glaucoma owing to abnormalities in the Schlemm’s canal and trabecular meshwork. Human ASD phenotypes are genetically heterogeneous,6 resulting from mutations in seven different transcription factor genes ( PAX6, PITX2, PITX3, FOXC1, FOXE3, …

To investigate spectral domain optical coherence tomography findings in long-term silicone oil-related visual loss.Four symptomatic patients were reviewed 4 years to 9 years after vitrectomy with silicone oil tamponade for macula-on retinal detachment. Three lost vision with oil in situ, with one at the time of oil removal. Eleven control eyes with good vision were included. Patients underwent assessment of best-corrected visual acuity, contrast sensitivity, Farnsworth-Munsell 100 Hue testing, static perimetry, and spectral domain optical coherence tomography imaging of the macula and disk.Long-term best-corrected visual acuity was significantly reduced in affected eyes (range, 0.44-1.02), as was contrast sensitivity (0.75-1.35) and color discrimination (Farnsworth-Munsell-100 Hue score, 151-390). Static perimetry showed a central scotoma in all affected eyes. Optical coherence tomography revealed microcystic macular changes in the inner nuclear layer of all affected eyes associated with severe loss of the papillofoveal retinal nerve fiber layer. In one patient, serial optical coherence tomography images showed development of microcystic macular changes 18 months after oil removal. Control eyes lacked these features, except two asymptomatic eyes that showed microcystic changes on optical coherence tomography with a corresponding paracentral scotoma.We have demonstrated microcystic macular changes in the inner nuclear layer of affected eyes, as well as focal severe loss of the papillofoveal projection. These changes share significant morphologic features reported in multiple sclerosis-associated optic neuritis and Leber hereditary optic neuropathy.

Bietti crystalline dystrophy is a rare autosomal recessive condition characterised by the presence of crystals in the retina and is followed by retinal and choroidal degeneration. We present a novel finding of juxtafoveal choroidal neovascularisation in Bietti crystalline dystrophy and demonstrate a spectral domain optical coherence tomography image of this disorder.

To prospectively investigate the safety and efficacy of a novel frequency-doubled nanosecond-pulsed laser with discontinuous beam energy distribution (2RT, Ellex) for the treatment of diabetic macular edema.Twenty-three consecutive patients (38 eyes) with newly diagnosed diabetic macular edema were recruited and assessed with logarithm of the minimum angle of resolution best-corrected visual acuity, central macular thickness measured with optical coherence tomography (OCT/scanning laser ophthalmoscope, OPKO/OTI), microperimetry, fundus photography, and fundus fluorescein angiography. Macular grid treatments were performed with 2RT laser system by 1 operator. Patients were examined with logarithm of the minimum angle of resolution best-corrected visual acuity, central macular thickness, microperimetry, and fundus photography at 3 weeks and 6 weeks and 3 months and 6 months. Fundus fluorescein angiography was repeated at 3 months and 6 months.Six months postoperatively, 17 patients (28 eyes) completed the study. No complications were identified after 2RT therapy. Intraoperative retinal discoloration was observed in 2 cases, fully resolved at 3 months with no permanent anatomical or functional changes. Mean logarithm of the minimum angle of resolution visual acuity improved from 20/44 at baseline to 20/27 at 6 months. The change in best-corrected visual acuity was significant (P = 0.0190). Central macular thickness in the central 1-mm subfield, retinal exudates and vascular leakage decreased in the majority of patients at 6 months (46, 41, and 55%, respectively), although the change from baseline was not statistically significant. Microperimetry confirmed photoreceptor integrity and showed a trend of improvement that correlated with decreased central macular thickness.For the first time, we achieved a beneficial effect on diabetic macular edema without the side effects of conventional laser therapy. The efficacy of this system in comparison with standard argon laser photocoagulation and in the treatment of other conditions affecting the retinal pigment epithelium needs further investigation.

To investigate whether three consanguineous families from the Punjab province of Pakistan, with affected members with recessively inherited congenital cataract microcornea with corneal opacity, are genetically homogeneous.An ophthalmic examination was performed on each family member to establish the diagnosis. The two largest families were analyzed by homozygosity mapping using SNP arrays. Linkage was confirmed using polymorphic microsatellite markers, and logarithm of odds (LOD) scores were calculated. Candidate genes were prioritized using the ENDEAVOUR program.Autosomal recessive congenital cataract-microcornea with corneal opacity mapped to chromosome 10cen for family MEP57 and to either chromosomes 2ptel or 20p for family MEP60. For MEP57, the refined interval was 36.8 Mb flanked by D10S1208 (35.3 Mb) and D10S676 (72.1 Mb). For MEP60, the interval containing the mutation was either 6.7 Mb from the telomere of chromosome 2 to marker D2S281 or 3.8 Mb flanked by D20S906 (1.5 Mb) and D20S835 (5.3 Mb). Maximum multipoint LOD scores of 3.09, 1.94, and 3.09 were calculated at D10S567, D2S281, and D20S473 for families MEP57 and MEP60. Linkage to these loci was excluded for family MEP68. SLC4A11 was excluded as a candidate gene for the observed phenotype in MEP60.The authors have identified two new loci, one on chromosome 10cen and the other on 2ptel or 20p, that are associated with recessively inherited congenital cataract-microcornea with corneal opacity. This phenotype is genetically heterogeneous in the Pakistani population. Further genetic studies of this kind, combined with a detailed phenotypic description, will contribute to more precise classification criteria for anterior segment disease.

Objectives To report the genetic basis of Leber congenital amaurosis (LCA) in northern Pakistan and to describe the phenotype. Methods DNA from 14 families was analyzed using single-nucleotide polymorphism and microsatellite genotyping and direct sequencing to determine the genes and mutations involved. The history and examination findings from 64 affected individuals were analyzed to show genotype-phenotype correlation and phenotypic progression. Results Homozygous mutations were found in RPGRIP1 (4 families), AIPL1 and LCA5 (3 families each), and RPE65 , CRB1 , and TULP1 (1 family each). Six of the mutations are novel. An additional family demonstrated linkage to the LCA9 locus. Visual acuity, severe keratoconus, cataract, and macular atrophy were the most helpful features in predicting the genotype. Many of the phenotypic variables became more prevalent with increasing age. Conclusions Leber congenital amaurosis in northern Pakistan is genetically heterogeneous. Mutations in RPGRIP1 , AIPL1 , and LCA5 accounted for disease in 10 of the 14 families. This study illustrates the differences in phenotype, for both the anterior and posterior segments, seen between patients with identical or different mutations in the LCA genes and also suggests that at least some of the phenotypic variation is age dependent. Clinical Relevance The LCA phenotype, especially one including different generations in the same family, may be used to refine a molecular diagnostic strategy.

Objective To describe new features and ocular coherence tomographic scans of individuals with West African crystalline maculopathy (WACM). Design Prospective observational case series. Participants All 14 patients with WACM identified in the medical retina clinic during a 6-month period. Methods Full ophthalmic examination and high-resolution ocular coherence tomographic imaging and fluorescein angiography where indicated. Main Outcome Measures Ethnicity and dietary history of individuals, location of crystals, and associated retinal comorbidity. Results Patients originated from several West African countries. Two patients had unilateral WACM. The crystals were yellow-green in color, birefringent, and located in the layer of Henle of the fovea. Coexistent retinal pathology was present in all patients. Conclusions Several new features of the condition are described. Breakdown of the blood retinal barrier may play a role in the formation of the crystals.

To describe the clinical features in a series of patients with poststreptococcal uveitis and to review literature on the pathophysiology and management.Retrospective and descriptive case series.Ten consecutive cases of poststreptococcal syndrome uveitis diagnosed between 1996 and 2003.Review of patient case notes.Age, laterality, clinical features, and anti-streptococcal lysin O titers.Ten consecutive cases of poststreptococcal syndrome uveitis were identified. All our cases had bilateral nongranulomatous inflammation and raised anti-streptococcal lysin O titers. Collating data from previous reports and this series showed that 96% of the patients were below 40 years of age, and 87.5% had evidence of previous streptococcal infection. One third of the patients had posterior segment involvement. In our patients, this was in the form of vitritis, focal retinitis, optic disc swelling, and multifocal choroiditis.Poststreptococcal syndrome uveitis should be considered in the etiology of acute bilateral nongranulomatous uveitis in children and young patients.

Leber's congenital amaurosis (LCA) is the most common cause of inherited childhood blindness and is characterised by severe retinal degeneration at or shortly after birth. We have identified a new locus, LCA9, on chromosome 1p36, at which the disease segregates in a single consanguineous Pakistani family. Following a whole genome linkage search, an autozygous region of 10 cM was identified between the markers D1S1612 and D1S228. Multipoint linkage analysis generated a lod score of 4.4, strongly supporting linkage to this region. The critical disease interval contains at least 5.7 Mb of DNA and around 50 distinct genes. One of these, retinoid binding protein 7 (RBP7), was screened for mutations in the family, but none was found.

We were interested to read the letter by Patel et al reporting the unusual and striking fundus appearance of retinal arteriolar calcification in association with chronic renal failure.1 However, we feel that two important conditions have been omitted from the comment, which merit further discussion. Firstly, Monckeberg’s sclerosis, which in its classic form is characterised by “pipe stem” calcific deposition in the medial coat of muscular …

Editor,—Congenital hereditary endothelial dystrophy (CHED) and posterior polymorphous corneal dystrophy (PPCD) are phenotypically distinct diseases of the corneal endothelium. Linkage analysis has mapped a locus for autosomal dominant PPCD to chromosome 20p11.1 Subsequently, other researchers placed a locus for autosomal dominant CHED (designated CHED1 by the human genome mapping workshop) in an overlapping genetic interval,2 suggesting that these two disorders may be allelic variants of the same defective gene. However, CHED is more commonly inherited as an autosomal recessive (AR) disease,3 and linkage analysis in a large consanguineous recessive Saudi Arabian pedigree excluded CHED1 as the causative locus.4 Genetic heterogeneity in this condition was further confirmed by linkage analysis in a large consanguineous Irish pedigree5 in which a second CHED genetic locus (CHED2) was subsequently localised more distally at 20p13.6 We now present a Pakistani pedigree with …