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Purpose: To evaluate the changes in peripapillary microvascularity in idiopathic intracranial hypertension (IIH) and optic disc drusen (ODD) patients, by comparing them with those in healthy individuals, via optical coherence tomography angiography (OCTA)., Methods: Sixty-two eyes of 33 patients with ODD, 58 eyes of 30 patients with IIH, and 70 eyes of 70 healthy people were imaged for 6 × 6-mm optic disc scans on a spectral-domain OCTA. Vascular densities in superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC) of ODD, IIH, and healthy eyes were compared with a one-way analysis of variance. Post-hoc analysis was performed with the Gabriel test., Results: There was a significant decrease in peripapillary vessel density in SCP, DCP, and CC in patients with IIH compared to the control group ( p  < 0.05). In ODD patients, especially peripapillary vessel density in DCP was significantly reduced compared to the control group ( p  < 0.05). Peripapillary vessel density in DCP was significantly lower in the IIH group than ODD group ( p  < 0.05)., Conclusions: Peripapillary vascular density may be affected during the course of the disease in both IIH and ODD. Compared to healthy individuals, the decrease in vascular density in these patients and the consequent decrease in perfusion in the peripapillary region may guide the pathogenesis of the complications in the course of these two diseases. Although vascular density in DCP and CC differs significantly between IIH and ODD, case-controlled studies are needed to evaluate the role of OCTA in the differential diagnosis of IHH and ODD., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Inherited retinal dystrophies (IRDs) as well as genetically complex retinal phenotypes represent a heterogenous group of ocular diseases, both on account of their phenotypic and genotypic characteristics. Therefore, overlaps in clinical features often complicate or even impede their correct clinical diagnosis. Deciphering the molecular basis of retinal diseases has not only aided in their disease classification but also helped in our understanding of how different molecular pathologies may share common pathomechanisms. In particular, these relate to dysregulation of two key processes that contribute to cellular integrity, namely extracellular matrix (ECM) homeostasis and inflammation. Pathological changes in the ECM of Bruch's membrane have been described in both monogenic IRDs, such as Sorsby fundus dystrophy (SFD) and Doyne honeycomb retinal dystrophy (DHRD), as well as in the genetically complex age-related macular degeneration (AMD) or diabetic retinopathy (DR). Additionally, complement system dysfunction and distorted immune regulation may also represent a common connection between some IRDs and complex retinal degenerations. Through highlighting such overlaps in molecular pathology, this review aims to illuminate how inflammatory processes and ECM homeostasis are linked in the healthy retina and how their interplay may be disturbed in aging as well as in disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Biasella, Plössl, Baird and Weber.)

EFEMP1 R345W is a dominant mutation causing Doyne honeycomb retinal dystrophy/malattia leventinese (DHRD/ML), a rare blinding disease with clinical pathology similar to age-related macular degeneration (AMD). Aged Efemp1  R345W/R345W knock-in mice (Efemp1ki/ki) develop microscopic deposits on the basal side of retinal pigment epithelial cells (RPE), an early feature in DHRD/ML and AMD. Here, we assessed the role of alternative complement pathway component factor B (FB) in the formation of these deposits. RNA-seq analysis of the posterior eyecups revealed increased unfolded protein response, decreased mitochondrial function in the neural retina (by 3 months of age) and increased inflammatory pathways in both neural retina and posterior eyecups (at 17 months of age) of Efemp1ki/ki mice compared with wild-type littermate controls. Proteomics analysis of eye lysates confirmed similar dysregulated pathways as detected by RNA-seq. Complement activation was increased in aged Efemp1ki/ki eyes with an approximately 2-fold elevation of complement breakdown products iC3b and Ba (P < 0.05). Deletion of the Cfb gene in female Efemp1ki/ki mice partially normalized the above dysregulated biological pathway changes and oral dosing of a small molecule FB inhibitor from 10 to 12 months of age reduced sub-RPE deposits by 65% (P = 0.029). In contrast, male Efemp1ki/ki mice had fewer sub-RPE deposits than age-matched females, no elevation of ocular complement activation and no effect of FB inhibition on sub-RPE deposits. The effects of FB deletion or inhibition on Efemp1ki/ki mice supports systemic inhibition of the alternative complement pathway as a potential treatment of dry AMD and DHRD/ML., (© The Author(s) 2022. Published by Oxford University Press. The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose of Review: The purpose of this review is to provide an overview of the ophthalmic findings associated with peripapillary hyperreflective ovoid mass-like structures (PHOMS) in both adult and pediatric patients., Recent Findings: PHOMS have recently been identified in a number of different ophthalmic disease entities ranging from nonpathologic to pathologic, including but not limited to anatomic abnormalities (tilting in myopia), optic nerve head drusen, optic disc edema from inflammation (optic neuritis, white dot syndromes), vascular insults (ischemic optic neuropathy, retinal vascular occlusion), and papilledema. The mechanism underlying the formation of PHOMS has not been fully elucidated although it has been hypothesized that PHOMS occur secondary to axoplasmic stasis from crowding at the optic nerve head., Summary: Although the clinical significance of the presence of PHOMS remains unclear, PHOMS are associated with several disease processes. Understanding the mechanism behind their formation and their impact on optic nerve head structure and visual function may be relevant in patients with optic nerve head pathology. The presence of PHOMS may also correlate with disease severity and duration. Future studies to evaluate whether the formation of PHOMS may be useful as an early indicator of disease or a prognostic tool are warranted., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To describe the clinical and genetic findings of patients in the second Japanese family with Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD)., Methods: Two patients (a 41-year-old male proband and his third son) underwent comprehensive ophthalmic examinations, including full-field and multifocal electroretinography (ERG). Sanger sequencing was performed to detect an EFEMP1 gene variant (p.Arg345Trp), which was identified as the only causative pathogenic variant., Results: Genetic analysis revealed that both patients carried the heterozygous variant, but the other unaffected family members did not. Although the proband exhibited innumerable radially distributed drusen in both the posterior poles and good visual acuity at initial presentation, bilateral choroidal neovascularization (CNV) developed during the 15-year follow-up. The proband received 15 intravitreal anti-vascular endothelial growth factor (VEGF) injections in the left eye (LE) and two injections in the right eye (RE). At 56 years of age, his decimal best-corrected visual acuity was 0.1 and 1.2 in the LE and RE, respectively. Full-field ERG showed that while the rod and combined responses were within normal amplitudes, the cone and 30-Hz flicker responses had slightly decreased amplitudes. Multifocal ERG revealed attenuated central responses in the LE and decreased temporal responses in the RE. In the 20-year-old son, multifocal ERG showed normal responses in both eyes., Conclusion: This is the first report of ML/DHRD in a patient who developed bilateral CNV and received anti-VEGF treatment in both eyes. Although multifocal ERG exhibited worsening of macular function, the generalized photoreceptor function was preserved until middle age., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To measure the serum levels of the oxidative stress markers superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GPx) and compare them before and after zinc supplementation in patients with early age-related macular degeneration (AMD). Methods: We measured serum zinc levels in 65 patients with early AMD. Of these, 29 patients with macular drusen and a serum zinc level <80 μg/dL received oral zinc acetate dihydrate (50 mg/day). Serum trace metal levels (zinc and copper) and oxidative stress marker levels (SOD, MDA, and GPx) were measured at baseline and 12 weeks after the treatment. The macular drusen areas and best-corrected visual acuity were evaluated in 24 participants who attended the 3-month follow-up. Results: MDA level was significantly decreased from baseline to 12 weeks after zinc administration (170.5 ± 100.9 vs. 148.3 ± 57.9 pmol/mL, P  = 0.03), while SOD was significantly increased from baseline to 12 weeks after zinc intake (4.2 ± 0.9 vs. 4.6 ± 0.9 U/mL, P  = 0.03). The serum zinc level was significantly correlated with the MDA level ( P  = 0.03, ρ = -0.26). The area of soft drusen was significantly decreased after zinc treatment (1,936,654.9 ± 1,348,267.6 vs. 966,883.9 ± 719,938.1 μmm 2 , P  = 0.04). Conclusions : The levels of oxidative stress markers MDA and SOD decreased and increased, respectively, after oral zinc administration to 24 patients with AMD. The therapeutic effect of zinc treatment on drusen area might differ depending on the drusen phenotype in early AMD.

Background: Doyne honeycomb retinal dystrophy (DHRD)/malattia leventinese (ML) is an autosomal dominant, progressive retinal disorder characterized by massive central retinal drusen often partly coalescent forming a characteristic honeycomb-like pattern. Debut of vision loss often occurs in early to mid-adulthood, and the degree varies. A single variant in EFEMP1: c.1033C>T (R345W) has been identified as the cause in all cases., Methods: Following DNA isolation, exome sequencing was performed in seven genes associated with flecked retina. Direct sequencing was used for variant verification., Results: We report the first Scandinavian case of molecular genetically verified DHRD/ML: a 57-year-old woman debuting with vision loss and metamorphopsia. On both eyes, ophthalmological findings included massive hard drusen in the macular region and nasal to the optic disc as well as macular hyperpigmentation. Secondary choroidal neovascularizations were identified on both eyes, and anti-vascular endothelial growth factor was administered, without effect., Conclusion: Molecular genetic investigation revealed heterozygosity for the known pathogenic missense variant in EFEMP1: c.1033C>T (R345W) previously reported in relation to DHRD/ML. Family history revealed no other cases of similar visual impairment suggesting a de novo mutation. Furthermore, there was no correlation between the unique DHRD/ML haplotypes reported in the literature and our patient., (© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Distinct mutations in the secreted extracellular matrix protein, fibulin-3 (F3), have been associated with a number of ocular diseases ranging from primary open angle glaucoma to cuticular age-related macular degeneration to a rare macular dystrophy, Malattia Leventinese (ML). The R345W F3 mutation that causes ML leads to F3 misfolding, inefficient secretion and accumulation at higher intracellular steady state levels in cultured cells. Herein, we determined whether fifteen other clinically-identified F3 mutations also led to similar levels of misfolding and secretion defects, which might provide insight into their potential pathogenicity. Surprisingly, we found that only a single F3 variant, L451F, presented with a significant secretion defect (69.5 ± 2.4% of wild-type (WT) F3 levels) and a corresponding increase in intracellular levels (226.8 ± 25.4% of WT F3 levels). Upon follow-up studies, when this conserved residue (L451) was mutated to a charged (Asp or Arg) or bulky (Pro, Trp, Tyr) residue, F3 secretion was also compromised, indicating the importance of small side chains (Leu, Ala, or Gly) at this residue. To uncover potential inherent F3 instability not easily observed under typical culture conditions, we genetically eliminated the sole stabilizing N-linked glycosylation site (N249) from select clinically-identified F3 mutants. This removal exacerbated R345W and L451F secretion defects (19.8 ± 3.0% and 12.4 ± 1.2% of WT F3 levels, respectively), but also revealed a previously undiscovered secretion defect in another C-terminal variant, Y397H (42.0 ± 10.1% of WT F3 levels). Yet, glycan removal did not change the relative secretion of the N-terminal mutants tested (D49A, R140W, I220F). These results highlight the uniqueness and molecular similarities between the R345W and L451F variants and also suggest that previously identified disease-associated mutations (e.g., R140W) are indistinguishable from WT with respect to secretion, hinting that they may lead to disease by an alternative mechanism.

To evaluate retrobulbar hemodynamics in patients with optic disc drusen (ODD) by color Doppler imaging. A prospective study included 52 patients with bilateral ODD and 50 age-matched controls. Blood flow in the central retinal artery (CRA) in both eyes was evaluated. Peak-systolic velocity (PSV), end-diastolic velocity (EDV), and the resistivity index (RI) were measured. Mean values of the blood flow Doppler parameters were compared between the patients with ODD and the controls. Both PSV and EDV in the CRA were significantly lower in patients with ODD than in the controls (p < 0.001). The RI in the CRA of ODD patients was significantly higher than in the controls (p < 0.001). Women with ODD presented with significantly lower values of PSV and EDV than men (p = 0.05 and p = 0.03, respectively). Arterial hypertension, cigarette smoking and location of ODD in the left or right eye did not exert a significant effect on the blood flow in the CRA. Blood flow in the CRA is considerably disturbed in patients with ODD. This disturbance might result from mechanical stenosis of the vascular wall caused by the drusen. Color Doppler ultrasound is a useful method in the assessment of retrobulbar hemodynamics in ODD.

Purpose: Optic disc drusen (ODD) are calcified optic nerve head deposits. Objectives of this study were to examine the prevalence of ODD in eyes removed by enucleation and to describe related histopathological signatures of ODD and surrounding tissues., Methods: The study was a retrospective observational case series study assessing and re-evaluating enucleated eyes in Denmark from 1980 to 2015 by microscopy. Individual ODD were described based on size, number and location (superficial and/or deep) within the optic nerve. Optic nerve heads with ODD were assessed for elevated discs, retinal nerve fibre layer (RNFL) thickness, oedematous axons and presence of localized peripapillary axonal distension (LPAD) equivalent to the peripapillary hyperreflective ovoid mass-like structures seen on optical coherence tomography., Results: Microscopy of 1713 eyes revealed ODD in 31 eyes equivalent to a prevalence of 1.8%. Optic disc drusen (ODD) were seen as circular shapes of different sizes and varying number. Elevated discs were present in 15 (54%) of the cases. Thickening of the superficial RNFL was present in eyes with large deeply located ODD. For more superficial ODD of approximately same size, the RNFL was thinner. Oedematous axons were present in three eyes. Localized peripapillary axonal distension (LPAD) was seen in five eyes., Conclusions: Prevalence of ODD in this study of histopathological signatures was higher than the prevalence found in clinical studies. Our results suggest that large, deep ODD might cause crowding and herniation of axons in the optic nerve head leading to a thickened superficial nerve fibre layer, pseudopapilledema and LPAD., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To investigate the prevalence and location of optic nerve head drusen and their potential association with other PXE-related ophthalmic abnormalities., Materials and Methods: Thirty-eight of the 155 patients (57 male and 98 female aged 49±17 years) included in this retrospective study had optic nerve head drusen. All of the patients underwent a comprehensive ophthalmic examination, including color images using red-free, blue and red filters, autofluorescence imaging and late-phase ICG frames. Comparative analysis of both groups (optic nerve head drusen or not) was conducted using R statistical software., Results: The prevalence of optic nerve head drusen in our cohort was 24.5%. In this study, no evidence of a significant link between optic nerve head drusen and other fundus abnormalities was detected. They were more commonly located in the nasal sector than in the temporal sector of the optic disc (P<0.001). They were more frequently situated superonasally than inferonasally (P<0.004), superotemporally (P<0.001) or inferotemporally (P<0.03). No central visual field defect was observed in OND+ patients who were unaffected by macular disorders., Discussion: We hypothesized this predominantly nasal primary location may result from greater sensitivity in the nasal optic nerve fibers which follow a much more angular path once they arrive in the scleral canal, accounting for accumulation of axoplasmic debris., Conclusion: In PXE, optic nerve head drusen are mostly located in the superonasal quadrant, causing progressive optic nerve invasion but probably no central visual field defects., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Peripapillary choroidal neovascularisation (PPCNV) associated with optic disc drusen is a rare complication that can result in severe vision impairment in children. We report the first case of paediatric PPCNV secondary to optic disc drusen successfully treated with intravitreal aflibercept. A 6-year-old girl presented with a one week history of reduced vision in her right eye with best-corrected visual acuity of 20/500. Fundus examination revealed bilateral elevated discs with a peripapillary pigmentary lesion in the right eye. Optical coherence tomography of the right eye showed marked subfoveal fluid. Both B-scan ultrasonography and fundus autofluorescence demonstrated findings consistent with optic disc drusen. Diagnosis of PPCNV was further confirmed on fluorescein fundus angiography. The child received three intravitreal aflibercept injections with complete resolution of the subfoveal fluid. Her visual acuity improved to 20/25 with no recurrence at a 16-month follow-up. No adverse side effects were reported., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Purposes: To correlate the clinical picture and fundus fluorescein angiography findings in case of presumed cutis marmorata telangiectatica congenita., Methods: A 41-year-old woman with presumed cutis marmorata telangiectatica congenita who is a known case of hypothyroidism for the last 6 years and has bilateral peripheral retinal vascular abnormalities, peripheral retinal nonperfusion on fluorescein angiography and bilateral optic disk drusen., Result: A patient presented with blurring of vision in both eyes for last 6 months. On examination, livedo reticularis skin lesions in both upper and lower extremities were noted. Best-corrected visual acuity in the right eye was 6/18 and left eye was 6/36. Slit-lamp examination revealed posterior subcapsular cataract in the right eye. Fundus examination showed bilateral optic disk drusen, tortuous blood vessels, and peripheral fan-shaped sclerosed neovascularization. Fundus fluorescein angiography showed peripheral retinal nonperfusion. She underwent peripheral laser photocoagulation of the left eye and cataract surgery in the right eye. After 2 years of follow-up, her best-corrected visual acuity was 6/9 in both eyes. Her fundus examination and fundus fluorescein angiography findings were stable in both eyes., Conclusion: Presumed cutis marmorata telangiectatica congenita is a rare cutaneous vascular disorder that can manifest with nonprogressive retinal vascular abnormality and optic disk drusen.

Purpose: To investigate the prevalence and risk factors for visual field defect in patients with optic disc drusen (ODD)., Methods: We assessed the visual field status of patients with ODD whose diagnosis were confirmed by spectral-domain optical coherence tomography (SD-OCT). Visual field defects were classified as normal, enlarged blind spot, or other defects. ODD were classified into either type 1 (without hyperreflective border and heterogenic internal reflectance) or type 2 (with hyperreflective border and lower internal reflectance). The prevalence and risk factors for each visual field defect was analyzed using logistic regression analysis and classification and regression tree (CART) modeling., Results: Of the 40 eyes with ODD, 33 (83%) eyes were categorized as type 1 and 7 (17%) eyes were categorized as type 2 ODD. Regarding the visual field defects, 19 (48%) eyes showed normal visual field, 11 (28%) eyes showed enlarged blind spot, and 9 (24%) eyes showed other defects. The latter was more frequent in type 2 ODD (P = 0.001). Logistic regression analysis revealed that the factor associated with other defects was the thinning of the average retinal nerve fiber layer (RNFL) (per 10 μm decrease, OR = 3.436, P = 0.004), and the factor associated with enlarged blind spot was the height of ODD (per 100 μm increase, OR = 3.956, P = 0.023). CART modeling revealed that the average RNFL thickness lesser than 85.5 μm, and then the ODD height larger than 348 μm were the best split-up factors for predicting the type of visual field defects., Conclusions: In this study, one-quarter of ODD patients showed abnormal visual field defect other than enlarged blind spot. These other visual field defects appeared to be associated with the axonal loss in the eyes with type 2 ODD.

Aim: To determine the efficacy of optical coherence tomography angiography (OCT-A) in diagnosing optic nerve head flow impairment in patients with optic nerve drusen., Methods: Patients affected by optic-nerve head drusen (ONHD) attending the Eye Clinic of the Federico II University of Naples were enrolled in this prospective case series between October 2015 and October 2016. Each patient underwent evaluation of best corrected visual acuity (BCVA), Goldman applanation tonometry, slit-lamp biomicroscopy, fundus examination, standard visual-field testing (perimetry), spectral domain (SD)-OCT and OCT-A., Results: Thirteen patients (6 females and 7 males with a mean age of 22.05 ± 7.54 years) with ONHD (19 eyes) were enrolled. Mean BCVA was 0.16 ± 0.21 LogMar and mean intraocular pressure was 15.68 ± 1.66 mm Hg. The control group constituted 16 individuals (24 eyes). Both ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL) parameters were lower in patients than in controls. Similarly, the flow index (U = 134, p = 0.021) and vessel density (U = 90, p = 0.001) were significantly lower in eyes affected by ONHD than in normal eyes. Visual-field parameters did not differ between the 2 groups. GCC parameters were significantly correlated with OCT-A parameters (p < 0.05). No correlation was found between RNFL and OCT-A parameters., Conclusions: Our data suggest that OCT-A could be an objective method, helpful in the analysis of flow changes in patients with ONHD., (© 2017 S. Karger AG, Basel.)

Differentiating optic disc edema (ODE) from pseudo optic disc edema (PODE) continues to pose a diagnostic dilemma. Current report highlights the role of multicolor imaging (MC) in differentiating ODE from PODE. Composite multicolor images of the disc in ODE show greenish hyperreflectance that extends beyond the optic disc margins with irregular blurry margins and obscured disc vasculature whereas PODE shows a greenish hyperreflectance with clear and distinct margins and well delineated disc vasculature. MC imaging adds to the present armamentarium of imaging modalities obviating needless neurological evaluation mandatory in a case of true disc edema.

Age-related macular degeneration (AMD) and related macular dystrophies (MDs) are a major cause of vision loss. However, the mechanisms underlying their progression remain ill-defined. This is partly due to the lack of disease models recapitulating the human pathology. Furthermore, in vivo studies have yielded limited understanding of the role of specific cell types in the eye vs. systemic influences (e.g., serum) on the disease pathology. Here, we use human induced pluripotent stem cell-retinal pigment epithelium (hiPSC-RPE) derived from patients with three dominant MDs, Sorsby's fundus dystrophy (SFD), Doyne honeycomb retinal dystrophy/malattia Leventinese (DHRD), and autosomal dominant radial drusen (ADRD), and demonstrate that dysfunction of RPE cells alone is sufficient for the initiation of sub-RPE lipoproteinaceous deposit (drusen) formation and extracellular matrix (ECM) alteration in these diseases. Consistent with clinical studies, sub-RPE basal deposits were present beneath both control (unaffected) and patient hiPSC-RPE cells. Importantly basal deposits in patient hiPSC-RPE cultures were more abundant and displayed a lipid- and protein-rich "drusen-like" composition. Furthermore, increased accumulation of COL4 was observed in ECM isolated from control vs. patient hiPSC-RPE cultures. Interestingly, RPE-specific up-regulation in the expression of several complement genes was also seen in patient hiPSC-RPE cultures of all three MDs (SFD, DHRD, and ADRD). Finally, although serum exposure was not necessary for drusen formation, COL4 accumulation in ECM, and complement pathway gene alteration, it impacted the composition of drusen-like deposits in patient hiPSC-RPE cultures. Together, the drusen model(s) of MDs described here provide fundamental insights into the unique biology of maculopathies affecting the RPE-ECM interface., Competing Interests: The authors declare no conflict of interest.

Introduction: Optic nerve head drusen are congenital calcium deposits located in the prelaminar section of the optic nerve head. Their association with visual field defects has been classically described, but the diagnosis of glaucoma is not easy in these cases of altered optic nerve head anatomy., Case Study: We describe the case of a 67-year-old man with optic nerve head drusen complicated by glaucoma, which was confirmed by visual field and OCT examination of the peripapillary retinal nerve fiber layer (RNFL), but the measurement of the minimum distance between the Bruch membrane opening and the internal limiting membrane (minimum rim width, BMO-MRW) by OCT was normal., Discussion: OCT of the BMO-MRW is a new diagnostic tool for glaucoma. Superficial optic nerve head drusen, which are found between the internal limiting membrane and the Bruch's membrane opening, overestimate the value of this parameter., Conclusion: BMO-MRW measurement is not adapted to cases of optic nerve head drusen and can cause false-negative results for this parameter, and the diagnosis of glaucoma in this case should be based on other parameters such as the presence of a fascicular defect in the retinal nerve fibers, RNFL or macular ganglion cell complex thinning, as well as visual field data., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Purpose: To describe new software tools for quantifying optic nerve head drusen volume using 3-dimensional (3D) swept-source optical coherence tomography (SS-OCT) volumetric scans., Materials and Methods: SS-OCT was used to acquire raster volume scans of 8 eyes of 4 patients with bilateral optic nerve head drusen. The scans were manually segmented by 3 graders to identify the drusen borders, and thereafter total drusen volumes were calculated. Linear regression was performed to study the relationships between drusen volume, retinal nerve fiber layer thickness, and Humphrey visual field mean deviation., Results: In the 8 study eyes, drusen volumes ranged between 0.24 to 1.05 mm. Visual field mean deviation decreased by ∼20 dB per cubic millimeter increase in drusen volume, and the coefficient of correlation of the linear regression was 0.92. In this small patient series, visual field defects were detected when drusen volume was larger than about 0.2 mm., Conclusions: Software tools have been developed to quantify the size of OHND using SS-OCT volume scans.

Purpose of Review: Mild papilledema may be difficult to distinguish by clinical observation from pseudopapilledema. An accurate diagnosis is critical to avoid invasive workup and unwarranted treatment. In this review, we focus on the development and subsequent role of optical coherence tomography (OCT) in detecting and differentiating optic nerve head drusen (ONHD) from papilledema and other causes of acquired swelling of the optic disc., Recent Findings: Newer OCT technologies which permit deeper penetration to improve detection of ONHD were also reviewed. Enhanced depth imaging (EDI) spectral-domain OCT and swept-source (SS) OCT are currently recognized as the most reliable and sensitive tools to diagnose ONHD. OCT devices currently available provide a means to quantify drusen dimensions, to evaluate the integrity of neighboring structures and to monitor axonal and neuronal damage, yielding additional information to better understand the relationship between the morphological features of drusen, and their effects on the structure and function of the optic nerve.

Correct differential diagnosis in cases of blurred optic disc margins is a challenging task for ophthalmologists. The reliable differentiation of pseudopapilloedema and true papilloedema has significant implications for proper patient management. Conditions that give rise to pseudopapilloedema include small crowded discs, tilted discs and optic nerve head drusen. Conditions that cause bilateral true swelling of the optic nerve head with initially good visual acuity include those that are secondary to raised intracranial pressure (optic disc edema, ODE). The majority of cases, however, present with unilateral optic nerve head swelling and normal intracranial pressure. They have systemic signs or symptoms which either precede ocular manifestation or have ophthalmoscopic signs other than elevation of the optic disc pointing to its diagnosis. Ancillary testing has been utilized to aid in identification of true ODE or swelling, including ultrasonography, fluorescein angiography, cranial and orbital MRI with venography, and lumbar puncture. Optical coherence tomography is also evolving as a modality for differentiation of buried optic disc drusen from ODE. This presentation will discuss each modality, with examples, advantages, and disadvantages for each., Competing Interests: Interessenkonflikt: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Optic disc drusen (ODD) are hyaline deposits located within the optic nerve head. Peripapillary retinal nerve fiber layer (RNFL) thinning is associated with the high prevalence of visual field defects seen in ODD patients. The goal of this study was to investigate the characteristics of patients with ODD and to compare the peripapillary RNFL thickness to the extent of visual field defects and anatomic location (superficial or buried) of ODD., Methods: Retrospective, cross sectional study., Results: A total of 149 eyes of 84 ODD patients were evaluated. Sixty-five percent were female and 76% had bilateral ODD. Of 149 eyes, 109 had superficial ODD and 40 had buried ODD. Peripapillary RNFL thinning was seen in 83.6% of eyes, where optical coherence tomography was performed (n = 61). Eyes with superficial ODD had greater mean peripapillary RNFL thinning (P ≤ 0.0001) and visual field defects (P = 0.002) than eyes with buried ODD. There was a correlation between mean peripapillary RNFL thinning and visual field defects as measured by perimetric mean deviation (R-0.66; P = 0.0001). The most frequent visual field abnormalities were arcuate and partial arcuate defects., Conclusions: Peripapillary RNFL thickness correlates with anatomic location (superficial or buried) of ODD. Frequency and extent of visual field defects corresponded with anatomic location of ODD and peripapillary RNFL thickness, suggesting increased axonal damage in patients with superficial ODD.

A 25-year-old man with X-linked retinoschisis presented with multiple giant optic nerve head drusen and multiple retinal drusenoid deposits in one eye. There was an area of coarse pigmentation in the lower half of the retina, with convex upper borders extending on either side of the optic disc, suggestive of a spontaneously resolved retinal detachment. The possible aetiopathogenesis of such occurrence is discussed., (2016 BMJ Publishing Group Ltd.)

Purpose: To evaluate the dynamic remodeling of drusen in subjects with unilateral neovascular age-related macular degeneration (AMD) receiving a three-year course of oral docosahexaenoic acid (DHA) or placebo., Setting: Institutional setting., Methods: Three hundred subjects with age-related maculopathy and neovascular AMD in the fellow eye were randomly assigned to receive either 840 mg/day DHA or placebo for 3 years. Main outcome measures of this post-hoc sub-group analysis were progression of drusen number, total diameter, and total area on fundus photography, and their association with DHA supplementation, socio-demographic and genetic characteristics., Results: Drusen progression was analyzed in 167 subjects that did not develop CNV (87 that received DHA and 80 that received placebo). None of the drusen remodeling outcomes were significantly associated with DHA supplementation. Total drusen diameter reduction in the inner subfield was significantly associated with age (older patients: r = -0.17; p = 0.003). Women showed a tendency to decreased total drusen diameter in the inner subfield with CFH polymorphism (p = 0.03), where women with TT genotype tended to have a greater reduction in drusen diameter than other genotypes (CC and CT). Drusen area in the inner subfield was more reduced in older patients (r = -0.17) and in women (p = 0.01). Drusen number showed no significant trends., Conclusions: Dynamic drusen remodeling with net reduction in drusen load over three years was found in patients with exudative AMD in one eye and drusen in the other eye (study-eye). This reduction was correlated with increased age and female gender, and showed a tendency to be influenced by CFH genotype, but did not appear to be affected by DHA supplementation., Trial Registration: Controlled-Trials.com ISRCTN98246501.

Cases Report: Two patients presented with headache and bilateral papillary edema. Patient 1 was found to have a papilledema (P) with intracranial pressure of 32cmH2O. Patient 2 was found to have a migraine with a pseudopapilledema (PP) (optic nerve head drusen). SD-OCT was used to image the optic disc, subretinal hyporeflective space (SHS), and alpha-angle (Aα)., Discussion: Optic disc SD-OCT may be useful for differentiating disc morphology in P and PP. The area of the SHS and the Aα were higher in the P patient than in the patient with PP., (Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: There are some reports showing isolated cases of drusen regression after pars plana vitrectomy (ppV) with peeling of the internal limiting membrane (iLM). Drusen characteristics after iLM peeling was investigated in this study., Patients and Methods: The data of 527 patients who had received iLM peeling between 2004 and 2012 were retrospectively collected and those patients with retinal drusen were selected for the study. Fundus photographs before and after vitrectomy due to a macular hole or epiretinal gliosis were compared and drusen arrangement in the peeling site was analyzed. The aim of the study was to show whether there was drusen regression 2-5 months after surgery., Results: Out of the 527 patients 11 showed central macular drusen, 4 with confluent large drusen (> 63 µm diameter) and 7 with small hard drusen (≤ 63 µm diameter). One patient showed drusen regression after iLM peeling without any changes in the other eye and all other patients showed no differences in the drusen findings (n = 6) or even some additional drusen (n = 4) without drusen alterations in the other eye., Conclusion: The results of this study could not confirm some reports showing drusen regression after iLM peeling in the peeling site in general and there was only one single case of central drusen regression.

Purpose: To describe the topography and predictors of peripapillary choroidal thickness (PPCT) in highly myopic eyes of young, healthy, Asian subjects., Methods: A total of 870 young male subjects aged 21.63 ± 1.15 years were recruited from the Singapore military. Choroidal imaging was performed using enhanced depth imaging (EDI) spectral-domain optical coherence tomography (SD-OCT). Peripapillary choroidal thickness was manually measured at eight locations around the optic disc., Results: We analyzed 448 subjects with high myopia (defined as spherical equivalent [SE] worse than -6.0 diopters [D]) and 116 with emmetropia (SE > -0.5 and < 0.5 D). The mean SE was -8.52 ± 1.20 D for the high-myopic group, and 0.11 ± 0.24 D for the emmetropic group. The mean peripapillary choroid was significantly thinner (142.62 ± 43.84 μm) in high myopes compared with emmetropes (181.90 ± 46.43 μm, P < 0.001). Likewise, PPCT showed further decrease with increase in degree of myopic refractive error. Distribution of PPCT showed a markedly different pattern in high-myopic eyes (thickest superiorly) and emmetropic eyes (thickest temporally). However, peripapillary choroid in both the groups was thinnest at the inferior location. Among the ocular factors studied, axial length, IOP, presence of posterior staphyloma, and chorioretinal atrophy were the factors significantly associated with PPCT., Conclusions: Highly myopic eyes have significantly thinner peripapillary choroid and showed different distribution of thickness, compared with emmetropes. Axial length, IOP, and presence of posterior staphyloma and chorioretinal atrophy significantly influence PPCT and should be taken into consideration during clinical interpretation of PPCT measurement., (Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.)

Purpose: To describe the clinical features of hemorrhagic complications secondary to optic nerve head drusen (ONHD) using spectral domain optical coherence tomography (SD-OCT)., Methods: Sixty-three consecutive patients with SD-OCT-documented ONHD who presented at Seoul National University Bundang Hospital from December 2009 to July 2012 were included. Full ophthalmologic examinations, including fundus photographs, SD-OCT, fundus angiography, and visual field tests were analyzed in a total of 101 ONHD-positive eyes from 63 patients., Results: Hemorrhagic ONHD complications were found in 7 eyes (7%) from a total of 101 eyes with ONHD. All of them had buried ONHD (visualized with SD-OCT) and myopia (mean spherical equivalent = -4.00 ± 2.35 diopters). Patients with ONHD hemorrhagic complications had smaller disk diameters than patients without hemorrhagic complications (1,308 ± 166 vs. 1,555 ± 217 μm, P = 0.004). Peripapillary hemorrhages were classified into the following 3 types based on SD-OCT findings: subretinal (6 eyes, 86%), retinal (5 eyes, 71%), and vitreous hemorrhage (4 eyes, 57%). Six patients (86%) complained of the recent onset of visual symptoms, but visual acuities at presentation were 20/20 in all patients. In the three patients who were followed up, most hemorrhages were absorbed without complications., Conclusion: Peripapillary hemorrhage can often occur in patients with buried ONHD and small disk diameters. As SD-OCT can be used to visualize ONHD beneath hemorrhage, it is helpful with the differential diagnosis and follow-up evaluation.

The aim of this study was to assess the feasibility of using a commercially available high-resolution adaptive optics (AO) camera to image the cone mosaic in Japanese macaques (Macaca fuscata) with dominantly inherited drusen. The macaques examined develop drusen closely resembling those seen in humans with age-related macular degeneration (AMD). For each animal, we acquired and processed images from the AO camera, montaged the results into a composite image, applied custom cone-counting software to detect individual cone photoreceptors, and created a cone density map of the macular region. We conclude that flood-illuminated AO provides a promising method of visualizing the cone mosaic in nonhuman primates. Future studies will quantify the longitudinal change in the cone mosaic and its relationship to the severity of drusen in these animals.

Spectral domain optical coherence tomography (SD-OCT) is a useful tool for the visualization of drusen, a retinal abnormality seen in patients with age-related macular degeneration (AMD); however, objective assessment of drusen is thwarted by the lack of a method to robustly quantify these lesions on serial OCT images. Here, we describe an automatic drusen segmentation method for SD-OCT retinal images, which leverages a priori knowledge of normal retinal morphology and anatomical features. The highly reflective and locally connected pixels located below the retinal nerve fiber layer (RNFL) are used to generate a segmentation of the retinal pigment epithelium (RPE) layer. The observed and expected contours of the RPE layer are obtained by interpolating and fitting the shape of the segmented RPE layer, respectively. The areas located between the interpolated and fitted RPE shapes (which have nonzero area when drusen occurs) are marked as drusen. To enhance drusen quantification, we also developed a novel method of retinal projection to generate an en face retinal image based on the RPE extraction, which improves the quality of drusen visualization over the current approach to producing retinal projections from SD-OCT images based on a summed-voxel projection (SVP), and it provides a means of obtaining quantitative features of drusen in the en face projection. Visualization of the segmented drusen is refined through several post-processing steps, drusen detection to eliminate false positive detections on consecutive slices, drusen refinement on a projection view of drusen, and drusen smoothing. Experimental evaluation results demonstrate that our method is effective for drusen segmentation. In a preliminary analysis of the potential clinical utility of our methods, quantitative drusen measurements, such as area and volume, can be correlated with the drusen progression in non-exudative AMD, suggesting that our approach may produce useful quantitative imaging biomarkers to follow this disease and predict patient outcome., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Purpose: To characterize longitudinal changes of reticular drusen (RDR) in subjects with geographic atrophy (GA) secondary to age-related macular degeneration in the multicenter, prospective natural history Geographic Atrophy Progression Study., Methods: Three-field confocal scanning laser ophthalmoscopy fundus autofluorescence (cSLO FAF, excitation [exc.] = 488 nm; emission [em.] 500-800 nm, Heidelberg Retina Angiograph/Spectralis) of 44 eyes of 22 patients with RDR (median age 77.6 years; range, 61-90 years) at baseline were identified in the study population and included for further analysis. Two independent readers determined the presence, topographic distribution, and pattern of RDR at baseline and at 18 months. Furthermore, the convex hull of the extent of RDR as the minimum polygon encompassing the entire area of RDR involvement was quantified., Results: RDR lesion boundaries were clearly detectable in all directions within three-field FAF composite images in 16 eyes of 10 patients at both baseline and final visits. Over time, RDR-affected retinal area and RDR density increased. Quantitative analysis showed a mean average RDR extent of 53.7 mm(2) (95% confidence interval [95% CI]; 40.7; 66.8) at baseline. The mean differences for intraobserver agreements were 2.4 mm(2) (95% CI; -0.1; 4.9) for reader 1 and -0.6 mm(2) (95% CI; -2.3; 1.1) for reader 2. The mean difference of interobserver agreement was 0.9 mm(2) (95% CI; -0.8; 2.7). A mean growth rate of the RDR extent within the three-field FAF composite image of 4.4 mm(2)/y (95% CI; 1.9; 6.9) was measured., Conclusions: In vivo cSLO FAF imaging allows for both qualitative and quantitative mapping of longitudinal changes of RDR areas within a relatively short time period. Continuous enlargement of the affected retinal area indicates disease progression with regard to this phenotypic characteristic associated with GA in AMD. Systematic recordings of RDR progression appears warranted in future natural history and interventional studies in dry AMD. (ClinicalTrials.gov number, NCT00599846.).

Purpose: To evaluate the morphologic characteristics of optic nerve head drusen., Design: Retrospective case series., Methods: setting: Institutional (Seoul National University Bundang Hospital). patients: Sixty-one patients with optic nerve head drusen. observation procedure: Visible and buried optic nerve head drusen were identified using funduscopy, whereas homogenous and nonhomogenous optic nerve head drusen were identified using spectral-domain optical coherence tomography images. Buried optic nerve head drusen were classified according to the size. main outcome measures: Classification of optic nerve head drusen., Results: Of 99 eyes in 61 patients, optic nerve head drusen were buried in 95 eyes and visible in 4 eyes. The patients with visible optic nerve head drusen were older on average than those with buried optic nerve head drusen (53.3 ± 8.6 years vs 13.5 ± 7.1 years; P < .001) and exhibited larger disc diameters (1643 ± 265 μm vs 1287 ± 185 μm; P = .016). All 4 eyes with visible optic nerve head drusen exhibited hyperreflective borders, which were not found in patients with buried optic nerve head drusen. Of 95 eyes with buried optic nerve head drusen, 64 eyes (67%) showed homogenous internal reflectivity, whereas 31 eyes (33%) showed nonhomogenous reflectivity with lobulations. Large optic nerve head drusen were associated with a small optic disc diameter, nonhomogenous internal reflectivity, a partial highly reflective border, intraretinal cysts, and increased temporal retinal nerve fiber layer thickness., Conclusions: Optic nerve head drusen have a diverse spectrum of spectral-domain optical coherence tomography findings associated with patient age and disc size., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: We compared the reproducibility and mutual agreement of the subfoveal choroidal thickness measurements by expert raters and an automated algorithm in enhanced depth imaging optical coherence tomography (EDI-OCT) images of eyes with nonneovascular age-related macular degeneration (AMD)., Methods: We recruited 44 patients with nonneovascular AMD and EDI-OCT images were acquired. Subfoveal choroidal thickness was measured manually by two expert raters and automatically by a graph-cut-based algorithm. Drusen area was measured using the automated software (version 6) of Cirrus SD-OCT. The manual and automated choroidal thickness measurements were compared in reproducibility, mutual agreement, and correlation with drusen area., Results: The mean subfoveal choroidal thickness was 246 ± 63 μm for the first rater, 214 ± 68 for the second rater, and 209 ± 53 for the automated algorithm. Intraclass correlation coefficients (ICC) and 95% confidence intervals (CI) were 0.96 (CI 0.94-0.98) between the raters, 0.85 (CI 0.77-0.90) between the first rater and the automated algorithm, and 0.84 (CI 0.75-0.89) between the second rater and the automated algorithm. Repeat scan measurement ICCs were 0.91 (CI 0.86-0.94) for the first rater, 0.96 (CI 0.94-0.97) for the second rater, and 0.87 (CI 0.80-0.92) for the automated algorithm. Manual and automated measurements were correlated with drusen area., Conclusions: The automated algorithm generally yielded smaller choroidal thickness than the raters with a moderate level of agreement. However, its repeat scan measurement repeatability was comparable to that of the manual measurements. The mean difference between the raters indicated possible biases in different raters and rating sessions. The correlation of the automated measurements with the drusen area was comparable to that of the manual measurements. Automated subfoveal choroidal thickness measurement has potential use in clinical practice and clinical trials, with possibility for reduced time and labor cost.

Purpose: To compare optic disc area measurement between optic nerve head drusen (ONHD) and control subjects using fundus photography, time-domain optical coherence tomography (TD-OCT) and spectral-domain optical coherence tomography (SD-OCT). We also made a comparison between each of the three techniques., Methods: We performed our study on 66 eyes (66 patients) with ONHD and 70 healthy control subjects (70 controls) with colour ocular fundus photography at 20º (Zeiss FF 450 IR plus), TD-OCT (Stratus OCT) with the Fast Optic Disc protocol and SD-OCT (Cirrus OCT) with the Optic Disc Cube 200 × 200 protocol for measurement of the optic disc area. The measurements were made by two observers and in each measurement a correction of the image magnification factor was performed. Measurement comparison using the Student's t-test/Mann-Whitney U test, the intraclass correlation coefficient, Pearson/Spearman rank correlation coefficient and the Bland-Altman plot was performed in the statistical analysis., Results: Mean and standard deviation (SD) of the optic disc area in ONHD and in controls was 2.38 (0.54) mm(2) and 2.54 (0.42) mm(2), respectively with fundus photography; 2.01 (0.56) mm(2) and 1.66 (0.37) mm(2), respectively with TD-OCT, and 2.03 (0.49) mm(2) and 1.75 (0.38) mm(2), respectively with SD-OCT. In ONHD and controls, repeatability of optic disc area measurement was excellent with fundus photography and optical coherence tomography (TD-OCT and SD-OCT), but with a low degree of agreement between both techniques., Conclusions: Optic disc area measurement is smaller in ONHD compared to healthy subjects with fundus photography, unlike time-domain and spectral-domain optical coherence tomography in which the reverse is true. Both techniques offer good repeatability, but a low degree of correlation and agreement, which means that optic disc area measurement is not interchangeable or comparable between techniques., (Ophthalmic & Physiological Optics © 2013 The College of Optometrists.)

Optic disc drusen (ODD) are benign calcified deposits, which are located at the head of the optic disc. Most ODD patients are asymptomatic. Ocular complications, related to ODD, are considered rare. Optic disc drusen, especially if it is bilateral, may mimic the clinical presentation of papilledema. The clinical discrimination between ODD and papilledema may be a challenging task, and in many cases, especially in the pediatric population, an ocular ultrasound examination is needed. A fundus examination, in order to rule out papilledema, is a common daily task for the ophthalmologist and is considered perhaps the most common interface between pediatricians, neurologists, internal physicians and ophthalmologists. In this review, we focused on the pathogenesis, epidemiology, diagnosis and clinical implications of ODD.

Purpose: To use three-dimensional optical coherence tomography (3D-OCT) to assess the prevalence of juxtapapillary retinal pigment epithelial detachments (jPED) in an asymptomatic population., Methods: Asymptomatic participants (i.e., family members of patients) were prospectively recruited over a 6-month period. Each subject completed a questionnaire prior to the acquisition of two undilated 45° fundus images and two undilated raster 3D-OCT scans (512 × 128) covering the macula and optic nerve from each eye using 3D-OCT-1000. Fundus images were graded for the presence of peripapillary atrophy (PPA), peripapillary pigment (PPP), drusen in the macula, and drusen elsewhere, whereas 3D-OCT scans were assessed for the presence of jPED, drusen in the macula, and drusen elsewhere., Results: In all, 276 eyes from 138 participants were evaluated. Mean participant age was 37.6 years (range: 18-74 years; SD: 15.5 years). In all, 87 jPEDs were detected in 26.1% (36/138) of asymptomatic participants (25 bilateral and 11 unilateral) or 17.0% (47/276) of asymptomatic eyes (23 in the right eye and 24 in the left). The maximum height of jPED was 198.3 ± 53.8 (range: 101.8-376.0) μm. The minimum distance of jPED to the border of optic nerve head (OPN) was 2.6 ± 11.1 (range: 0-61.9) μm. The occurrence of jPEDs or drusen elsewhere by subjects increased statistically with increasing age (P < 0.001, respectively)., Conclusions: In this study, definite jPEDs were observed by OCT in asymptomatic participants, which were not seen with fundus photography. jPEDs were seen more commonly with increasing age, although it is not known whether these lesions represent deposition of drusen-like material or aborted choroidal neovascularization adjacent to the natural break in Bruch's membrane at the optic disc.

Purpose: To evaluate the effect of lysosomal destabilization on NLRP3 inflammasome activation in RPE cells and to investigate the mechanisms by which inflammasome activation may contribute to the pathogenesis of age-related macular degeneration (AMD)., Methods: Human ocular tissue sections from patients with geographic atrophy or neovascular AMD were stained for NLRP3 and compared to tissues from age-matched controls. Expression of the IL-1β precursor, pro-IL-1β, was induced in ARPE-19 cells by IL-1α treatment. Immunoblotting was performed to assess expression of NLRP3 inflammasome components (NLRP3, ASC, and procaspase-1) and pro-IL-1β in ARPE-19 cells. Lysosomes were destabilized using the lysosomotropic agent L-leucyl-L-leucine methyl ester (Leu-Leu-OMe). Active caspase-1 was detected using FAM-YVAD-FMK, a fluorescent-labeled inhibitor of caspases (FLICA) specific for caspase-1. IL-1β was detected by immunoblotting and ELISA, and cytotoxicity was evaluated by LDH quantification., Results: RPE of eyes affected by geographic atrophy or neovascular AMD exhibited NLRP3 staining at lesion sites. ARPE-19 cells were found to express NLRP3, ASC, and procaspase-1. IL-1α dose-dependently induced pro-IL-1β expression in ARPE-19 cells. Lysosomal destabilization induced by Leu-Leu-OMe triggered caspase-1 activation, IL-1β secretion, and ARPE-19 cell death. Blocking Leu-Leu-OMe-induced lysosomal disruption with the compound Gly-Phe-CHN(2) or inhibiting caspase-1 with Z-YVAD-FMK abrogated IL-1β release and ARPE-19 cytotoxicity., Conclusions: NLRP3 upregulation occurs in the RPE during the pathogenesis of advanced AMD, in both geographic atrophy and neovascular AMD. Destabilization of RPE lysosomes induces NLRP3 inflammasome activation, which may contribute to AMD pathology through the release of the proinflammatory cytokine IL-1β and through caspase-1-mediated cell death, known as "pyroptosis."

We report two cases of atypical temporal arteritis. A 73-year-old woman with typical internal (diabetes, hypertony, hypercholesterinemia) and ophthomological (optic disc drusen) risk factors for N-AION reported with an acute unilateral decrease in vision. General symptoms, laboratory analysis and biopsy led to the diagnosis of temporal arteritis and iv steroids were administered. An 83-year-old male patient reported with a sudden unilateral decrease in vision, but did not complain about general symptoms. Laboratory analysis revealed no signs for temporal arteritis, therefore the patient was referred to his internal specialist for evaluation of internal risk factors for N-AION. A few days later the patient reported with a unilateral decrease in vision of the partner eye. This time blood analysis was suggestive of temporal arteritis although no general symptoms were reported. Diagnosis was supported by a biopsy of the temporal artery and steroids were administered. These two cases teach us how dangerously easy temporal arteritis can be overlooked and that we have to take even the slightest hint for temporal arteritis seriously and initiate treatment as early as possible., (Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: To evaluate optic nerve head (ONH) parameters, peripapillary retinal nerve fiber layer (RNFL) thickness, and macular thickness by using Cirrus HD spectral-domain optical coherence tomography (OCT) in young patients with retinitis pigmentosa (RP)., Methods: ONH parameters, RNFL thickness, and macular thickness were measured and compared between 36 eyes from 36 young RP patients (RP group; mean age, 23.08 years) and 70 eyes from 70 healthy young subjects (control group; mean age, 22.66 years) using Cirrus HD-OCT. The effects of the presence of optic disc pallor and the severity of visual field (VF) defects on OCT parameters were also evaluated., Results: The RP group had a greater rim area, smaller cup-to-disc ratio, smaller cup volume, thicker RNFL, and thinner macula than the control group (p ≤ 0.024). ONH parameters were not affected by the presence of optic disc pallor (p ≥ 0.239). Eyes with more severe VF defects (mean deviation ≤ -13.88 dB) had thinner average macular areas than eyes with less severe VF defects (mean deviation ≥ -13.88 dB; p = 0.002). Meanwhile, the ONH parameters and average peripapillary RNFL thickness were not significantly different between the two groups (p ≥ 0.275)., Conclusions: Young eyes with RP exhibited different OCT parameters compared to healthy eyes. Among the various OCT parameters, only macular thickness was associated with disease severity. These findings should be considered when evaluating young RP patients.

Background: To evaluate the morphological features and prevalence of accompanying late age-related macular degeneration (AMD) according to the fundus distribution of reticular pseudodrusen (RPD)., Methods: According to the involved area in the fundus, the distribution of RPD was classified as localised, intermediate, or diffuse type. Morphology of RPD was classified as discrete, branching, or confluent pattern. The presence of late AMD was evaluated., Results: 233 eyes of 121 patients with RPD were included. The distribution of RPD was localised, intermediate and diffuse type in 30.9%, 40.3% and 28.8% of eyes, respectively. The discrete, branching and confluent morphological patterns were found in 45.8%, 44.8% and 9.7% of the localised type, and in 0%, 13.8% and 86.2% of the intermediate type, respectively. In contrast, the diffuse type showed only the confluent morphological pattern. The prevalence of accompanying late AMD was 13.9%, 13.8% and 56.7% in the localised, intermediate and diffuse type, respectively, and it was significantly higher in the diffuse type (p<0.05)., Conclusion: RPD with diffuse distribution showed a confluent morphological pattern and a high prevalence of late AMD. RPD can be classified by the fundus distribution for the assessment of visual prognosis.

Purpose: The aim of this study was to investigate the relationship between clinical macular changes and retinal function in age-related macular degeneration (AMD)., Methods: We recruited 357 participants with visual acuity of better than 20/60 in the study eye, including 64 individuals with normal fundi and 293 AMD participants classified into 12 subgroups based upon the International Classification and Grading System. Visual function in the study eye was assessed using two steady-state tests (achromatic 14 Hz flicker [F14Hz] and isoluminant blue color [BCT]) and two adaptation measurements (cone photo-stress recovery rate [CRR] and rod dark adaptation recovery rate [RRR]). The groups were compared on their average psychophysical measurements and ranked according to functional deficiency., Results: Both adaptation parameters were significantly abnormal when only hard and/or intermediate drusen were evident (compared to controls, P < 0.023) and yielded considerably worse outcomes in cases with more advanced fundus changes (P < 0.001), but provided limited ability to discriminate between these cases (linear trend, CRR t = 0.68, P = 0.50 and RRR t = 1.76, P = 0.08). Steady-state measurements, however, declined gradually along the entire hierarchy of fundus changes (linear trend, F14Hz t = 10.16, P < 0.001 and BCT t = 11.19, P < 0.001) with F14Hz being able to detect significant functional change as early as in the intermediate drusen group, when compared to controls (P = 0.003)., Conclusions: Steady state thresholds (F14Hz and BCT) and clinical signs showed significant concordance across the spectrum of early AMD fundus changes. This suggests that these tests may be an effective tool for monitoring progression of AMD to supplement clinical grading.

The question as to why the macula of the retina is prone to an aging disease (age-related macular degeneration) remains unanswered. This unmet challenge has implications since AMD accounts for approximately 54% of blindness in the USA (Swaroop, Chew, Bowes Rickman and Abecasis, 2009). While AMD has onset in the elder years, it likely develops over time. Genetic discovery to date has accounted for approximately 50% of the inheritable component of AMD. The polymorphism that has been most widely studied is the Y402H allele in the complement factor H gene. The implication of this genetic association is that in a subset of AMD cases, unregulated complement activation is permissive for AMD. Given that this gene variant results in an amino acid substitution, it is assumed that this change will have functional consequences although the precise mechanisms are still unknown. Genetic predisposition is not the only factor however, since in this complex disease there is substantial evidence that lifestyle factors such as diet and smoking contribute to risk. Here we provide an overview of current knowledge with respect to factors involved in AMD pathogenesis. Interwoven with these issues is a discussion of the significant role played by aging processes, some of which are unique to the retina and retinal pigment epithelium. One recurring theme is the potential for disease promotion by diverse types of oxidation products., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Purpose: Using the Retro-mode (RM), to detect drusen and other minute lesions of the retinal pigment epithelium (RPE) invisible in current imaging methods in the fellow eye of Japanese patients with exudative age-related macular degeneration(AMD)., Design: A retrospective cross-sectional study., Patients and Methods: The fellow eyes of nineteen Japanese patients with unilateral exudative AMD were examined using RM imaging (F-10 fundus camera, Nidek), in contrast with fluorescein angiography, indocyanine green angiography, and optic coherence tomography (3D OCT-1000, Topcon Co). We were able to identify the type of drusen and minute granular lesions (MGLs) in the RPE., Results: In all patients, RM imaging gave easier to identify images of all types of drusen than other current imaging methods. Moreover, MGLs of the RPE either adjacent to drusen or without drusen, invisible in other current methods, were detected by RM imaging., Conclusions: The RM provides clearer imaging of all kind of drusen, and MGLs of the RPE invisible with current methods. These MGLs are possible precursors of drusen.

Purpose: The purpose of this study was to describe the association of acquired vitelliform lesion (AVL) and large drusen in patients with non-neovascular age-related macular degeneration., Methods: A retrospective review of clinical examination and multimodal imaging data of patients with AVL and large drusen seen over a 12-month period was performed. Acquired vitelliform lesion was defined as subretinal accretion of hyperautofluorescent yellowish material within the macular region not due to vitelliform macular dystrophy. Large drusen were diagnosed by the presence of mounded deposits in the subretinal pigment epithelial space between the retinal pigment epithelium and the Bruch membrane using multimodal imaging analysis (color photography, autofluorescence, and spectral domain optical coherence tomography)., Results: Thirteen eyes of 9 white patients with a mean age of 74 years were observed to have AVL associated with large drusen. The median visual acuity was 20/60. All AVLs were hyperautofluorescent and were located in the subretinal space between the retinal pigment epithelium and the photoreceptor inner segment/outer segment junction. The AVL in this series had similar color, autofluorescence, and optical coherence tomographic findings as the AVL seen in association with cuticular drusen and subretinal drusenoid deposits., Conclusion: Acquired vitelliform lesions, which have previously been related to cuticular drusen and subretinal drusenoid deposits, can occur in association with large drusen. Abnormalities leading to drusen formation or processes that function in parallel to these may be causative in AVL formation.

Purpose: To report a new sporadic case of membrane frizzled-related protein gene (MFRP)-related syndrome with a 30-month follow-up, and to review the literature for genotype-phenotype correlation in MFRP mutations., Methods: A complete ophthalmological evaluation was performed at presentation and 30 months later, including best-corrected visual acuity test, slit lamp examination, fundoscopy, kinetic perimetry, electroretinography, fundus imaging (color, red-free, and autofluorescence), and morphologic-biometric analysis of the eye structures with an optical biometer, anterior-segment optical coherence tomography, retinal optical coherence tomography, and a confocal scanning laser for optic nerve head study. Polymerase chain reaction amplification of DNA obtained from peripheral blood lymphocytes and nucleotide sequencing of the complete MFRP gene were performed. The literature on cases of posterior microphthalmos and retinitis pigmentosa associated with MFRP mutations was reviewed., Results: A 33-year-old female patient presented with posterior microphthalmos, retinitis pigmentosa with patches of retinal pigmented epithelium atrophy and scarce pigment mobilization, foveoschisis, and optic nerve drusen. After 30 months, progression of rod-cone retinal degeneration was detected. One obligate carrier showed a normal eye phenotype. A homozygote mutation in the MFRP gene (c.492delC), predicting a truncated protein (P166fsX190), was identified with genetic analysis. To our knowledge, 17 cases of MFRP-related syndrome have been reported in the literature, including the patient described herein. The phenotype of the syndrome, expressivity, and age of onset varied among and within the affected families. However, all patients sharing homozygous mutation c.492delC (alternatively named c.498delC) showed a complete phenotype (including foveoschisis and optic nerve head drusen), and similar fundus characteristics., Conclusions: A new sporadic case of MFRP-related syndrome is reported. Review of the literature showed variability in the phenotype, but initial elements of genotype-phenotype correlation have been identified in patients sharing the mutation of the present case.