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To present the observation of multifocal evanescent white dot syndrome (MEWDS)-like phenotypes developing in association with the onset of choroidal neovascularization (CNV) in a series of patients.Patients presenting to tertiary-care centers with MEWDS-like phenotypes and CNV were identified.Five patients presented for the management of CNV in the context of previous diagnoses of punctate inner choroidopathy (PIC) and/or myopia. In time-periods ranging from 0 days to 12 weeks from the diagnosis of active CNV, MEWDS-like changes were observed. Treatment with anti-VEGF agents were instituted in four cases, in an as-required protocol. 1 patient received systemic steroid.The development of MEWDS-like phenotypes in association with CNVM can occur in eyes with either inflammatory or non-inflammatory CNVM, and in those who were or were not treated with anti-VEGF therapy. The association suggests an inflammatory event, which causes RPE changes and probably induces the development of the CNV.

Persistent anterior uveitis causing cystoid macular oedema may necessitate either intraocular or systemic immunosuppression. This case report highlights how a newly licenced treatment, fluocinolone acetonide (Iluvien®, Alimera Sciences Ltd., England, UK) achieves quiescence in refractory and steroid-dependent disease and in the presence of an acute relapse.

A 58-year-old Afro-Caribbean gentleman with a diagnosis of quiescent systemic lupus erythematosus- (SLE-) related occlusive retinal vasculitis was previously treated with sector pan-retinal photocoagulation in his right eye to control temporal retinal neovascularization. At routine review he was found to have a focal area of subretinal fluid in the temporal macula sparing an ischaemic fovea. Fundus fluorescein angiography and indocyanine green angiography confirmed a branching vascular network (BVN) and terminal polys (i.e., polypoidal choroidal vasculopathy (PCV)). Interestingly, the BVN arose within an old laser scar. To our knowledge this is the first report of PCV in uveitis in an Afro-Caribbean patient and of the lesions arising within a laser scar.

PurposeThe aim of this study was to determine a sequence of structural changes in acute posterior multifocal placoid pigment epitheliopathy (APMPPE) using optical coherence tomography-angiography (OCT-A) and comparing with other imaging modalities.Patients and methodsPatients with a new diagnosis of acute-onset APMPPE referred to a regional specialist centre from October 2015 to October 2016 were included. Multimodal imaging employed on all patients from diagnosis included the following: fundus fluorescein angiography, indocyanine green angiography, fundus autofluorescence, spectral domain-OCT (SD-OCT), and OCT-A. All non-invasive imaging processes were repeated during follow-up.ResultsTen eyes of five patients were included in the study, three males and two females, with a mean age of 26.2 years (range: 21–32) and a mean follow-up of 6.4 months (range: 2.6–13.3). All patients presented with bilateral disease and macular involving lesions. OCT-A imaging of the choriocapillaris was supportive of hypoperfusion at the site of APMPPE lesions during the acute phase of this condition with normalisation of choroidal vasculature during follow-up. Multimodal imaging consistently highlighted four sequential phases from presentation to resolution of active disease.ConclusionsMultimodal imaging in patients with APMPPE in acute and long-term follow-up demonstrates a reversible choroidal hypoperfusion supporting the primary inciting pathology as a choriocapillaritis. The evolution shows resolution of the ischaemia through a defined sequence that results in persistent changes at the level of the retinal pigment epithelium and outer retina. OCT-A was able to detect preclinical changes and chart resolution at the level of the choriocapillaris.

BACKGROUND/OBJECTIVES To determine if the presence of sub-retinal fluid (SRF) was associated with reduced vision in dome-shaped macula (DSM), and to assess its effect and response to treatment during follow-up. METHODS Patients were identified retrospectively. Baseline and follow-up data were recorded. The diagnosis of DSM, and presence or absence of SRF and intra-retinal fluid (IRF) was confirmed using Spectral Domain-Optical Coherence Tomography (SD-OCT). Decisions to treat oedema were based on clinician preference. RESULTS 193 eyes of 106 patients (71 female) were confirmed to have DSM. Overall mean duration of follow-up for this cohort was 3.5 years. Mean BRVA for all eyes at baseline was 0.38 (range: -0.20 to 'light perception'). A significant difference was noted in mean baseline BRVA between those eyes with SRF compared with those without SRF at baseline (0.48 vs. 0.31, p

Acute macular neuroretinopathy (AMN) is a rare disease, the etiology of which remains unclear. An ischemic event at the level of the deep capillary plexus has been proposed. The authors present three cases of AMN in the context of active systemic Behçet's disease, with the support of multimodal imaging. All patients were known to have Behçet's disease before the diagnosis of AMN. AMN was confirmed in all three cases on spectral domain optical coherence tomography (SD-OCT), near infrared reflectance and OCT angiography. Behçet's disease is known to be a prothrombotic disease. The presentation of AMN in this context supports the presumed ischemic etiology of AMN. [ Ophthalmic Surg Lasers Imaging Retina . 2018;49:634–638.]

The purpose of our study was to investigate morpho-functional features of the preferred retinal location (PRL) and the transition zone (TZ) in a series of patients with recessive Stargardt disease (STGD1). Fifty-two STGD1 patients with at least one ABCA4 mutation, atrophy of the central macula (MA) and an eccentric PRL were recruited for the study. Microperimetry, fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT) were performed. The location and stability of the PRL along with the associated FAF pattern and visual sensitivities were determined and compared to the underlying retinal structure. The mean visual sensitivity of the PRLs for the 52 eyes was 10.76 +/- 3.70 dB. For the majority of eyes, PRLs were associated with intact ellipsoid zone (EZ) bands and qualitatively normal FAF patterns. In 17 eyes (32.7%) the eccentric PRL was located at the edge of the MA. In 35 eyes (67.3%) it was located at varying distances from the border of the MA with a TZ between the PRL and the MA. The TZ was associated with decreased sensitivity values (5.92 +/- 4.69 dB) compared to PRLs (p

Purpose To determine whether intraocular lens (IOL) exchange with insertion of a sulcus-fixated IOL is an effective treatment for the management of pseudophakic negative dysphotopsia. Setting Department of Ophthalmology, Stoke Mandeville Hospital, Buckinghamshire, United Kingdom. Design Case series. Methods Participants in the study were recruited prospectively from the clinic at the time of diagnosis or retrospectively from the operating room logs by identifying all patients who had IOL exchanges over a 4-year period (2009 to 2012). Results Five eyes of 5 women with negative dysphotopsia were treated with IOL exchange and replacement with a 3-piece IOL (Acrysof MA60AC) inserted in the ciliary sulcus. All patients had a resolution of the negative dysphotopsia symptoms. One patient had primary insertion of a sulcus IOL in the fellow eye and did not develop negative dysphotopsia symptoms. Conclusion Intraocular lens exchange with insertion of a 3-piece IOL in the ciliary sulcus appears to be a safe and effective treatment for the management of pseudophakic negative dysphotopsia. Financial Disclosure Neither author has a financial or proprietary interest in any material or method mentioned.

Background: A 71-year-old female presented on 3 occasions with escalating pain in a congenitally blind eye. Examination revealed hypertensive uveitis with morning glory optic disc dysplasia and absence of a crystalline lens. There was no previous intraocular surgery or trauma. Intensive anti-hypertensive agents and topical steroids did not control intraocular pressure (IOP) or inflammation. Results: Dilated fundus examination on the third clinical review revealed a luxated cataractous lens on the retina. Pars plana vitrectomy and fragmatome lensectomy controlled inflammation and IOP, with resolution of ocular pain. Discussion: This is an exceptional case of phacogenic uveitis with secondary glaucoma occurring years after spontaneous crystalline lens luxation in a patient with morning glory syndrome. The embryological pathogenesis of morning glory syndrome and the significance of accelerated cataractogenesis and zonular weakness are discussed. Hypertensive uveitis with unexplained absence of a crystalline lens in a blind eye must prompt suspicion of delayed phacogenic uveitis following asymptomatic lens luxation.

PURPOSE. We evaluated the pathogenicity of the G1961E mutation in the ABCA4 gene, and present the range of retinal phenotypes associated with this mutation in homozygosity in a patient cohort with ABCA4-associated phenotypes. METHODS. Patients were enrolled from the ABCA4 disease database at Columbia University or by inquiry from collaborating physicians. Only patients homozygous for the G1961E mutation were enrolled. The entire ABCA4 gene open reading frame, including all exons and flanking intronic sequences, was sequenced in all patients. Phenotype data were obtained from clinical history and examination, fundus photography, infrared imaging, fundus autofluorescence, fluorescein angiography, and spectral domain-optical coherence tomography. Additional functional data were obtained using the full-field electroretinogram, and static or kinetic perimetry. RESULTS. We evaluated 12 patients homozygous for the G1961E mutation. All patients had evidence of retinal pathology consistent with the range of phenotypes observed in ABCA4 disease. The latest age of onset was recorded at 64 years, in a patient diagnosed initially with age-related macular degeneration (AMD). Of 6 patients in whom severe structural (with/ without functional) fundus changes were detected, 5 had additional, heterozygous or homozygous, variants detected in the ABCA4 gene. CONCLUSIONS. Homozygous G1961E mutation in ABCA4 results in a range of retinal pathology. The phenotype usually is at the milder end of the disease spectrum, with severe phenotypes linked to the presence of additional ABCA4 variants. Our report also highlights that milder, late-onset Stargardt disease may be confused with AMD. (Invest Ophthalmol Vis Sci. 2012; 53:4458–4467) DOI:10.1167/iovs.11-9166

Since the discovery of the ABCA4 gene as the cause of autosomal recessive Stargardt disease/fundus flavimaculatus much has been written of the phenotypic variability in ABCA4 retinopathy. In this review the authors discuss the findings seen on examination and the disease features detected using various clinical tests. Important differential diagnoses are presented and unusual presentations of ABCA4 disease highlighted.

Stargardt disease (STGD1) is caused by mutations in the ABCA4 gene. It has previously been reported that abnormalities in STGD1 may be detectable in the photoreceptors using spectral domain-optical coherence tomography (SD-OCT) prior to the detection of retinal pigment epithelium abnormalities. We present a 5-year-old asymptomatic girl with normal appearing fundi who possessed pathogenic ABCA4 variants on both chromosomes and where thickening of the external limiting membrane was the only abnormality detected on SD-OCT.

Purpose To describe pathologic changes of the external limiting membrane (ELM) in young patients with early-onset Stargardt (STGD1) disease. Methods Twenty-six STGD1 patients aged younger than 20 years with confirmed disease-causing adenosine triphosphate-binding cassette, subfamily A, member 4 (ABCA4) alleles and 30 age-matched unaffected individuals were studied. Spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (AF), and color fundus photography (CFP) images, as well as full-field electroretinograms were obtained and analyzed for one to four visits in each patient. Results The ELM in all patients exhibited a distinct thickening that was not observed in unaffected individuals. In addition, accumulations of reflective deposits were noted in the outer nuclear layer in every patient. Four patients exhibited a concave protuberance or bulging of a thickened and hyperreflective ELM band within the fovea containing preserved photoreceptors. Longitudinal SD-OCT data in several patients revealed the persistence of this ELM abnormality over a period of time (1-4 years). Furthermore, the edges of the inner segment ellipsoid band appeared to recede earlier than the ELM band in active lesions. Conclusions Structural changes seen in the ELM of this cohort may reflect a gliotic response to cellular stress at the photoreceptor level in early-onset STGD1.

Objective To report a new phenotype caused by mutations in the CRB1 gene in a family with 2 affected siblings. Design Molecular genetics and observational case studies. Participants Two affected siblings and 3 unaffected family members. Methods Each subject received a complete ophthalmic examination together with color fundus photography, fundus autofluorescence (FAF), and spectral-domain optical coherence tomography (SD-OCT). Microperimetry 1 (MP-1) mapping and electroretinogram (ERG) analysis were performed on the proband. Screening for disease-causing mutations was performed by whole exome sequencing in 3 family members followed by segregation analyses in the entire family. Main Outcome Measures Appearance of the macula as examined by clinical examination, fundus photography, FAF imaging, SD-OCT, and visual function by MP-1 and ERG. Results The proband and her affected brother exhibited unusual, previously unreported, findings of a macular dystrophy with relative sparing of the retinal periphery beyond the vascular arcades. The FAF imaging showed severely affected areas of hypoautofluorescence that extended nasally beyond the optic disc in both eyes. A central macular patch of retinal pigment epithelium (RPE) sparing was evident in both eyes on FAF, whereas photoreceptor sparing was documented in the right eye only using SD-OCT. The affected brother presented with irregular patterns of autofluorescence in both eyes characterized by concentric rings of alternating hyper- and hypoautofluorescence, and foveal sparing of photoreceptors and RPE, as seen on SD-OCT, bilaterally. After negative results in screening for mutations in candidate genes including ABCA4 and PRPH2 , DNA from 3 members of the family, including both affected siblings and their mother, was screened by whole exome sequencing resulting in identification of 2 CRB1 missense mutations, c.C3991T:p.R1331C and c.C4142T:p.P1381L, which segregated with the disease in the family. Of the 2, the p.R1331C CRB1 mutation has not been described before and the p.P1381L variant has been described in 1 patient with Leber congenital amaurosis. Conclusions This report illustrates a novel presentation of a macular dystrophy caused by CRB1 mutations. Both affected siblings exhibited a relatively well-developed retinal structure and preservation of generalized retinal function. An unusual 5-year progression of macular atrophy alone was observed that has not been described in any other CRB1 -associated phenotypes.

In retinal degenerative diseases, there is a transition zone (TZ)1–3 between relatively normal retina containing healthy photoreceptors and severely affected retina with extreme photoreceptor atrophy. Through the use of frequency-domain optical coherence tomography (fdOCT), the TZ can now be visualized and quantitatively assessed.1,2 A better understanding of the TZ is of importance for two reasons. First, knowledge of which retinal layers are affected across the TZ will aid in determining the potential efficacy and optimal injection locations for gene therapy.1,4 Second, the TZ offers a potential model of disease progression. That is, it is plausible to assume that the sequence and nature of structural changes observed spatially across the TZ at one specific time (that of fdOCT acquisition) also occur at each location in the retina as the disease progresses over time. Thus far, fdOCT studies of the TZ have been limited mainly to retinitis pigmentosa (RP) and Usher syndrome.1,2 A consistent pattern of changes in the outer retina has emerged from these studies. Specifically, Hood et al.2 found that structural damage (thinning) in RP occurs first in the outer segment (OS) layer and then in the outer nuclear layer (ONL), but that retinal pigment epithelium (RPE) thickness remains relatively normal across the TZ. This pattern is consistent with the disease process associated with many genetic forms of RP, where the defect often originates with an abnormal OS protein. Our main purpose in the present study was to determine whether the pattern of changes in the photoreceptor/RPE layers within the TZ differs in the various diseases that affect the receptors. That is, to what extent is the pattern of loss specific to the disease entity? To answer this question, we chose two disease entities, one, like RP, which typically starts outside the fovea, and one that starts within the fovea. Choroideremia (CHM), an X-linked retinal disorder, causes degeneration of the choroid and outer retina. Because of the nature of the progression of this disease, beginning in the midperiphery and moving centrally, patients with CHM typically have a central retina that is both structurally and functionally near normal, but the peripheral retina is severely affected. This pattern is similar to the pattern often seen in patients with RP. Stargardt disease (STGD), an autosomal recessive disorder, is a form of juvenile macular degeneration characterized by atrophy of the retinal pigment epithelium (RPE) and photoreceptor layer. In contrast to CHM and RP, STGD usually first affects the central retina and then progresses toward the periphery. Thus, patients with STGD typically have a diseased central retina with loss of central vision, but a near-normal peripheral retina. TZs are therefore present between the healthier and affected regions in both CHM and STGD. Given that CHM is considered to be allied to RP and that the two diseases are sometimes confused because of their common symptoms of night blindness and progressively decreasing peripheral vision,5,6 there are reasons to believe that their TZs are similar. However, some studies have shown that photoreceptor degeneration in CHM occurs secondary to, or at least concurrently with, atrophy of the RPE and choriocapillaris.7–10 RPE atrophy, induced by lipofuscin accumulation, is a main feature of STGD, although there is disagreement as to whether photoreceptor loss occurs before or after the RPE is affected.3,11–14 Therefore, there are also reasons to expect some differences in the sequence and occurrence of structural changes of the RPE and photoreceptor layer across the three diseases. In the present study, the thicknesses of fdOCT layers associated with the OS, ONL, and RPE were quantified in 7 patients with CHM and 20 with STGD, and the results were compared to each other and to our previously reported results for patients with RP.2

To describe the spectral domain-optical coherence tomography (SD-OCT) findings of two patients with complete defects in the retinal pigment epithelium (RPE) with disruptions in Bruch membrane in Stargardt disease (STGD1).Two patients with STGD1 were referred to our clinic for further evaluation. Fundus autofluorescence (FAF), spectral domain optical coherence tomography (SD-OCT), electroretinography (ERG) and Microperimetry (MP-1) were performed to assess the retinal anatomy and function. Screening for mutations in the ABCA4 gene was carried out and detected mutations were confirmed by direct sequencing.Both patients had bilateral macular geographic atrophy (GA) and yellowish subretinal pisciform flecks and mutations were detected in the ABCA4 gene by chip screening. SD-OCT revealed marked atrophy of the retina in the central macula, with focal defects in the RPE with disruptions in Bruch membrane and herniation of the retina through the defect in three of four eyes.This case report highlights the necessity for a detailed ophthalmic examination including SD-OCT of patients with STGD1.

Mutations in the ABCA4 gene are responsible for a wide variety of retinal dystrophy phenotypes, such as autosomal recessive Stargardt disease (STGD1),1 cone-rod dystrophy (CRD),2,3 and retinitis pigmentosa (RP).2,4,5 STGD1 (Mendelian Inheritance in Man 248200) is a predominantly juvenile-onset macular dystrophy associated with rapid central visual impairment, progressive bilateral atrophy of the foveal retinal pigment epithelium (Fig. 1), and frequent appearance of yellowish flecks, defined as lipofuscin deposits, around the macula or in the central and near-peripheral areas of the retina. In a large fraction of STGD1 patients, a “dark ” or “silent ” choroid is seen on fluorescein angiography that reflects the accumulation of lipofuscin throughout the retina. Figure 1. Fundus autofluorescence image of the left eye of patient 3032 harboring ABCA4 variants c.2300T>A (p.V767D) and c.735T>G (p.Y245*). This combination of ABCA4 mutations resulted in early disease onset at 5 years of age. At 16 years of age, ... More than 600 disease-associated ABCA4 variants have been identified,6 and the most frequent disease-associated ABCA4 alleles have each been described in only approximately 10% of STGD1 patients. Several studies have identified frequent “ethnic group-specific” ABCA4 alleles, such as the c.2588G>C variant resulting in a dual effect, p.G863A/delG863, as a founder mutation in Northern European patients with STGD17 and a complex allele (two variants on the same chromosome), p.L541P/A1038V, in both STGD1 and CRD patients of German origin (Fig. 2B).3,8 Complex ABCA4 alleles are not uncommon in STGD1.9 In fact, they are detected in approximately 10% of all STGD patients.10 Figure 2. Pedigrees segregating Stargardt disease. (A) An example of a pedigree with pseudodominant inheritance. Father and son are both affected with arSTGD. Mother is a carrier of a frequent c.3322C>T (p.R1108C) mutation. The new c.3522+5delG variant ... Allelic heterogeneity has substantially complicated genetic analyses of ABCA4-associated retinal disease. Efforts related to mutation detection and genotyping become especially crucial in genotype/phenotype correlation studies, in which screening of thousands of samples is needed to achieve enough statistical power because multiple rare variants and their combinations must be studied.11 We generated, at the time, a high-throughput and cost-effective screening tool, the ABCA4 genotyping microarray,12 using solid-phase arrayed primer extension (APEX) technology. The ABCA4 microarray, which has been regularly updated, contains all known disease-associated genetic variants (>600) in the ABCA4 gene. The chip has been used for efficient, systematic screening of patients with ABCA4-associated diseases13,14; it detects approximately 65% to 75% of all disease-associated alleles. On average, the array screening finds two mutations in approximately 40% of patients diagnosed with “classical” STGD1. Of the rest, one mutation is detected in 40% of patients, whereas no disease-associated allele is found in the ABCA4 coding region in 20% of screened patients.6 Direct Sanger sequencing of the entire ABCA4 coding region detects between 66% and 80% of the alleles10,15 but remains prohibitive for large patient cohorts because of time and cost constraints. Studies assessing the fraction of copy number variant (CNV) mutations, which elude PCR-based methods such as direct sequencing, (e.g., large deletions of exons and chromosomal segments), have found these in only approximately 1% of all STGD1 patients.16 Overall, variation in the ABCA4 locus has emerged as the most prevalent cause of Mendelian retinal disease because approximately 1 of 20 people across all populations carry a potential disease-associated variant in this gene.7,12,15 Recent advances in developing therapeutic applications for STGD1 in preclinical studies17,18 suggest that more comprehensive and affordable genetic screening technologies have to be implemented for molecular diagnosis and for selection of patients who would benefit from specific (especially gene-based) therapeutic modalities. Here we describe screening by NGS of a large cohort of ABCA4-associated patients who had been analyzed by the ABCA4 array and still lacked one or both mutations.

Mutations in the ABCA4 gene are the known cause of autosomal recessive Stargardt disease (STGD1).1 The ABCA4 protein is the transporter of vitamin A derivatives in the outer segment disc membranes of photoreceptors. In the absence of functional protein due to mutations in the gene, vitamin A aldehyde forms bis-retinoid adducts that are deposited in retinal pigment epithelial (RPE) cells during the process of disc shedding and phagocytosis. One of the features of ABCA4 disease is relative peripapillary sparing, characterized by the absence of flecks and RPE atrophy in the peripapillary region of the retina.2–5 The presence of either is termed peripapillary atrophy. Recent reports have shown that a small percentage of patients with STGD1 develop peripapillary atrophy.6,7 We have demonstrated peripapillary atrophy using fundus autofluorescence (FAF) in patients classified as ERG group II or III STGD1.8 The classification was based on full-field electroretinogram (ERG) results. Patients with a normal scotopic and photopic ERGs are classified as group I).9 Patients with ERG group II disease have decreased photopic ERGs, whereas patients with ERG group III disease have decreased scotopic and photopic ERGs.9 In our previous study, 1 of 15 patients in group I, all 7 patients in group II, and 9 of 10 patients in group III demonstrated peripapillary atrophy.8 Because of the relative sparing of the peripapillary area in ABCA4 disease, it has been suggested that this is a region of interest for monitoring the efficacy of treatment in this disease.2 Therefore detailed structural and functional characterization of this retinal region is of interest. Whereas previous methods of assessing the peripapillary retina have focused on its appearance using en face imaging,2–5,8 we used spectral-domain optical coherence tomography (SD-OCT) to evaluate the integrity of the outer retinal layers and RPE and microperimetry to assess visual function in this region and across the macula. Both modalities use retinal tracking features to compensate for eye movement during examination, a feature essential in assessing ABCA4 disease phenotypes with reduced visual acuity and unstable fixation.

Purpose To describe and correlate the features of astrocytic hamartomas using multimodal imaging. Design Prospective, noncomparative, observational case series. Methods This was a single-center study of 4 patients (8 eyes) with tuberous sclerosis complex. A complete ophthalmologic examination, fundus photography, fundus autofluorescence (FAF), infrared imaging, and spectral-domain optical coherence tomography (SD-OCT) were performed for each patient. Images from each modality were analyzed and compared. Results In 2 patients, infrared imaging and SD-OCT detected occult retinal astrocytic hamartomas that were not observed on clinical examination or color fundus photography. FAF demonstrated the greatest contrast between lesions and surrounding retina but failed to identify 1 occult lesion that was detected with infrared imaging and SD-OCT. SD-OCT revealed lesions arising from the retinal nerve fiber layer with overlying vitreous adhesions, hyperreflective dots, and optically empty spaces at all depths of the tumor. Hamartomas were hyporeflective on infrared imaging and hypoautofluorescent on FAF. FAF of some lesions demonstrated hyperautofluorescent spots. Conclusions Infrared imaging and SD-OCT aid in the detection of astrocytic hamartomas that are not visible on clinical examination or color fundus photography. SD-OCT enhances visualization of structural details. FAF is a useful adjunctive test to obtain greater contrast between lesions and surrounding retina. The ability to monitor structural changes over time in astrocytic hamartomas using SD-OCT may be beneficial for monitoring the success of systemic chemotherapy in the treatment of various tuberous sclerosis tumors.

To quantify fundus autofluorescence (qAF) in patients with recessive Stargardt disease (STGD1).A total of 42 STGD1 patients (ages: 7-52 years) with at least one confirmed disease-associated ABCA4 mutation were studied. Fundus AF images (488-nm excitation) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to account for variable laser power and detector sensitivity. The gray levels (GLs) of each image were calibrated to the reference, zero GL, magnification, and normative optical media density to yield qAF. Texture factor (TF) was calculated to characterize inhomogeneities in the AF image and patients were assigned to the phenotypes of Fishman I through III.Quantified fundus autofluorescence in 36 of 42 patients and TF in 27 of 42 patients were above normal limits for age. Young patients exhibited the relatively highest qAF, with levels up to 8-fold higher than healthy eyes. Quantified fundus autofluorescence and TF were higher in Fishman II and III than Fishman I, who had higher qAF and TF than healthy eyes. Patients carrying the G1916E mutation had lower qAF and TF than most other patients, even in the presence of a second allele associated with severe disease.Quantified fundus autofluorescence is an indirect approach to measuring RPE lipofuscin in vivo. We report that ABCA4 mutations cause significantly elevated qAF, consistent with previous reports indicating that increased RPE lipofuscin is a hallmark of STGD1. Even when qualitative differences in fundus AF images are not evident, qAF can elucidate phenotypic variation. Quantified fundus autofluorescence will serve to establish genotype-phenotype correlations and as an outcome measure in clinical trials.

A 45 year old man was referred to the medical team with a one week history of unilateral headache associated with nausea and photophobia. Simple analgesia proved ineffective. His symptoms were relieved only by draping a towel over his eyes and head while avoiding movement. He usually had three or four self described “migraines” a year but said “this was the worst ever” and that he felt generally unwell. On examination, he had marked epiphora in his right eye. Visual acuity was reduced to hand movements and the pupil was fixed and mid-dilated. Severe corneal oedema made funduscopy impossible. His left eye was white with visual acuity of 6/6. There was no fever or signs of meningism. Routine blood tests were unremarkable and a computed tomogram of the head was within normal limits. The patient, who is of Middle Eastern descent, was normally fit and well and did not use regular drugs. He had no ocular history and denied trauma to the eye. He did not wear glasses. ### 1 What is the most likely diagnosis? #### Short answer Acute primary angle closure glaucoma (APACG). #### Long answer The presenting symptoms of nausea, headache, and photophobia are non-specific but can be indicative of serious neurological disease that requires urgent investigation and intervention. Subarachnoid haemorrhage and meningitis both deserve consideration, as well as some of the headache syndromes such as migraine and cluster headache. Although common to many neurological conditions, the patient’s symptoms could also have an ophthalmic cause so history taking and an appropriate examination are essential. Indeed, on closer questioning it may transpire that what was initially described as a headache is actually retro-orbital or ocular pain. Failure to consider ophthalmic disease properly and to clearly …

Purpose To evaluate the constriction of the hyperautofluorescent ring over time in patients with retinitis pigmentosa (RP). Design Prospective study. Methods Fourteen eyes of 14 RP patients with a hyperautofluorescent ring were studied. Ring constriction was evaluated by measurements of its external and internal boundaries along the vertical and horizontal axes at baseline and at 12-, 24-, 36-, and 48-month follow-ups. Repeat fundus autofluorescence was obtained at 12, 24, 36, and 48 months in 13, 7, 5, and 1 eyes respectively. Spectral-domain optical coherence tomography (SD-OCT) images were obtained on 8 eyes and the horizontal extent of the inner segment/outer segment (IS/OS) junction was measured. SD-OCT was repeated at 12 and 24 months in 6 and 4 eyes respectively. Results The external boundaries of the ring were identified along the horizontal axis in 12 eyes and along the vertical axis in 13. Internal boundaries were identified in 7 eyes. Constriction was demonstrated in all patients except 1 who demonstrated minimal expansion of the internal boundary along the horizontal axis. SD-OCT measurements showed a decrease in the IS/OS junction length. Conclusion Progressive constriction of the hyperautofluorescent ring and a concordant decrease in IS/OS junction length were observed over time.