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To assess the relationship of demographics, clinical characteristics and structural optical coherence tomography (OCT) findings to long-term visual outcomes in patients with Leber hereditary optic neuropathy (LHON) treated with idebenone.Retrospective, interventional, noncomparative clinical cohort study.In this study, a total of 17 participants (34 eyes) with LHON treated with idebenone therapy within 1 year after disease onset and 2 years (24 months) of regular follow-ups were retrospectively enrolled. At baseline, structural OCT volume scans of the macula and optic nerve were reviewed to measure metrics reflecting neuronal loss (ie, macular ganglion cell and inner plexiform layer [GC-IPL] and peripapillary retinal nerve fiber layer [RNFL] thicknesses). Stepwise multiple regression analyses were computed to assess associations between final best-corrected visual acuity (BCVA) at 2 years and change in BCVA from baseline at 2 years as dependent variables with demographics, clinical characteristics, and OCT metrics at baseline (visit before the initiation of treatment).The BCVA was 1.6±0.8 logMAR (Snellen VA of ∼20/800) at baseline (visit before the initiation of treatment) and 1.0±0.7 logMAR (Snellen VA of 20/200) at the 2-year follow-up visit (P.0001). Mean±SD change in BCVA from baseline at 2 years was -51.9%±35.9%. In multivariable analysis, the strongest associations with final BCVA were with baseline BCVA (P = .012), superior macular GC-IPL thickness (P = .044), superotemporal macular GC-IPL thickness (P = .010), and inferotemporal macular GC-IPL thickness (P = .015). Similarly, the strongest associations with delta BCVA were with superior macular GC-IPL thickness (P = .045), superotemporal macular GC-IPL thickness (P = .047), and inferotemporal macular GC-IPL thickness (P = .030).We identified OCT biomarkers associated with long-term (ie, 2-year) visual outcomes in patients with LHON treated with idebenone therapy in the first year after disease onset. Thinning of the GC-IPL in the superior and temporal parafoveal regions was associated with worse long-term visual outcomes in these patients.

PURPOSE: To describe the clinical phenotype of a cohort of patients with Wolfram syndrome (WS), focusing on the pattern of optic atrophy correlated with brain magnetic resonance imaging (MRI) measurements, as compared with patients with OPA1-related dominant optic atrophy (DOA).center dot DESIGN: Retrospective, comparative cohort study.center dot METHODS: We reviewed 25 patients with WS and 33 age-matched patients affected by OPA1-related DOA. Ophthalmologic, neurologic, endocrinologic, and MRI data from patients with WS were retrospectively retrieved. Ophthalmologic data were compared with data from patients with OPA1-related DOA and further analyzed for age dependency dividing patients in age quartiles. In a subgroup of patients with WS, we correlated the structural damage assessed by optical coherence tomography (OCT) with brain MRI morphologic measurements. Visual acuity (VA), visual field mean defect (MD), retinal nerve fiber layer (RNFL), and ganglion cell layer (GCL) thickness were assessed by OCT and MRI morphologic measurements of anterior and posterior visual pathways.center dot RESULTS: Optic atrophy was present in 100% of patients with WS. VA, MD, and RNFL thickness loss were worse in patients with WS with a faster decline since early age as compared with patients with DOA, who displayed a more stable visual function over the years. Conversely, GCL sectors were overall thinner in patients with DOA since early age compared to patients with WS, in which GCL thickness started to decline later in life. The neuroradiologic subanalysis on 11 patients with WS exhibited bilateral thinning of the anterior optic pathway, especially the prechiasmatic optic nerves and optic tracts. Optic tract thinning was significantly correlated with GCL thickness but not with RNFL parameters.center dot CONCLUSIONS: Our results showed a generally more severe and diffuse degeneration of both anterior and posterior visual pathways in patients with WS, with fast deterioration of visual function and structural OCT parameters since early age. The pattern observed with OCT suggests that retinal ganglion cell axonal degeneration (ie, RNFL) precedes cellular body atrophy (ie, GCL) by about a decade. This differs substantially from DOA, in which a more stable visual function is evident with predominant early loss of GCL, indirectly supporting the lack of a primary mitochondrial dysfunction in patients with WS. (Am J Ophthalmol 2022;241: 206-216. (c) 2022 Elsevier Inc. All rights reserved.)

To investigate the clinical and molecular genetic features of childhood-onset Leber hereditary optic neuropathy (LHON) to gain a better understanding of the factors influencing the visual outcome in this atypical form of the disease.Retrospective cohort study.We retrospectively included two cohorts of LHON patients with onset of visual loss before the age of 12 years old from Italy and the United Kingdom. Ophthalmological evaluation, including best-corrected visual acuity, orthoptic evaluation, slit-lamp biomicroscopy, visual field testing and optical coherence tomography (OCT) were considered. Patients were classified based both on the age of onset and the pattern of visual loss.68 PATIENTS WERE STRATIFIED BASED ON THE AGE OF ONSET OF VISUAL LOSS: GROUP 1 (3YRS): : 14 patients (20.6%); Group 2 (≥ 3 -9yrs): 27 patients (39.7%); and Group 3 (≥ 9 - ≤ 12yrs): 27 patients (39.7%). Patients in Group 2 achieved a better visual outcome compared with those in Group 3. Patients in Group 1 and Group 2 had better mean deviation on visual field testing compared with those in Group 3. The mean ganglion cell layer thickness on OCT was higher in Group 2 compared with those in Group 1 and Group 3. Patients were also categorized based on the pattern of visual loss as: Subacute Bilateral: 54 patients (66.7%); Insidious Bilateral: 14 patients (17.3%); Unilateral: 9 patients (11.1%); and Subclinical Bilateral: 4 patients (4.9%).Children who lose vision from LHON before the age of 9 years old have a better visual prognosis compared with those who become affected in later years, likely representing a "form frustre" of the disease.

Objective Dominant optic atrophy (DOA) is the most common inherited optic neuropathy, with a prevalence of 1:12,000 to 1:25,000. OPA1 mutations are found in 70% of DOA patients, with a significant number remaining undiagnosed. Methods We screened 286 index cases presenting optic atrophy, negative for OPA1 mutations, by targeted next generation sequencing or whole exome sequencing. Pathogenicity and molecular mechanisms of the identified variants were studied in yeast and patient-derived fibroblasts. Results Twelve cases (4%) were found to carry novel variants in AFG3L2, a gene that has been associated with autosomal dominant spinocerebellar ataxia 28 (SCA28). Half of cases were familial with a dominant inheritance, whereas the others were sporadic, including de novo mutations. Biallelic mutations were found in 3 probands with severe syndromic optic neuropathy, acting as recessive or phenotype-modifier variants. All the DOA-associated AFG3L2 mutations were clustered in the ATPase domain, whereas SCA28-associated mutations mostly affect the proteolytic domain. The pathogenic role of DOA-associated AFG3L2 mutations was confirmed in yeast, unraveling a mechanism distinct from that of SCA28-associated AFG3L2 mutations. Patients' fibroblasts showed abnormal OPA1 processing, with accumulation of the fission-inducing short forms leading to mitochondrial network fragmentation, not observed in SCA28 patients' cells. Interpretation This study demonstrates that mutations in AFG3L2 are a relevant cause of optic neuropathy, broadening the spectrum of clinical manifestations and genetic mechanisms associated with AFG3L2 mutations, and underscores the pivotal role of OPA1 and its processing in the pathogenesis of DOA. ANN NEUROL 2020 ANN NEUROL 2020;88:18-32.

We previously documented that idebenone treatment in OPA1‐Dominant Optic Atrophy (OPA1‐DOA) led to some degrees of visual improvement in seven patients. We here present the results of a cohort study, which investigated the effect of off‐label idebenone administration in a larger OPA1‐DOA group compared with untreated patients. Inclusion criteria were: OPA1‐DOA clinical and molecular diagnosis, baseline visual acuity (VA) greater than/equal to counting fingers and treatment duration greater than 7 months. We found a significant difference between the last visit and baseline VA in favor of stabilization/recovery in idebenone‐treated as compared to untreated patients. This effect was retained after controlling for confounders.

Journal: INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Invest Ophthalmol Vis Sci. 2022 Jan 3;63(1):43. doi: 10.1167/iovs.63.1.43. PMID: 35098304; PMCID: PMC8802032 Abstract Purpose:The purpose of this study was to evaluate optic disk perfusion and neural retinal structure in patients with subacute Leber's hereditary optic neuropathy (LHON) and LHON carriers, as compared with healthy controls. Methods:This study included 8 patients with LHON in the subacute stage, 10 asymptomatic carriers of a LHON-associated mitochondrial DNA mutation, and 40 controls. All subjects underwent measurement of the retinal nerve fiber layer (RNFL) thickness, the ganglion cell-inner plexiform layer (GCIPL) thickness using optical coherence tomography and optic disk microvascular perfusion (Mean Tissue [MT]) using laser speckle flowgraphy (LSFG). Patients were re-examined after a median interval of 3 months from the baseline visit. Results:LHON carriers had higher values of RNFL thickness, GCIPL thickness, and disk area than controls (P < 0.05), whereas MT was not different between the two groups (P = 0.936). Median MT and RNFL thickness were 32% and 15% higher in the early subacute stage of the disease than in controls (P < 0.001 and P = 0.001). MT declined below the values of controls during the late subacute stage (P = 0.024), whereas RNFL thickness declined later during the dynamic stage (P < 0.001). GCIPL thickness was lower in patients with LHON than in controls independently of the stage of the disease (P < 0.001). Conclusions:The high blood flow at the optic disk during the early subacute stage may be the consequence of vasodilation due to nitric oxide release as compensation to mitochondrial impairment. Optic disk perfusion as measured by LSFG is a promising biomarker for LHON diagnosis and monitoring as well as an objective outcome measure for assessing response to therapies.

To capture the key features patterning the transition from unaffected mutation carriers to clinically affected Leber hereditary optic neuropathy (LHON), as investigated by optical coherence tomography.Observational case series.Four unaffected eyes of 4 patients with LHON with the first eye affected were followed across conversion to affected, from 60 days before to 170 days after conversion. The primary outcome measures were multiple timepoints measurements of peripapillary retinal nerve fiber layer (RNFL) thickness for temporal emi-side of the optic nerve (6 sectors from 6-11, clockwise for the right eye and counterclockwise for the left eye) in all patients and nasal emi-macular RNFL and ganglion cell layer (GCL) thickness in 2 patients.While the presymptomatic stage was characterized by a dynamic thickening of sector 8, the beginning of the conversion coincided with an increase in the thickness of the sectors bordering the papillo-acular bundle (6 and 7 for the inferior sectors, 10 and 11 for the superior sectors) synchronous with the thinning of sectors 8 and then 9. Conversely, the GCL did not undergo significant changes until the onset of visual loss when a significant reduction of thickness became evident.In this study we demonstrated that the thinning of sector 8 can be considered the structural hallmark of the conversion from the presymptomatic to the affected state in LHON. It is preceded by its own progressive thickening extending from the optic nerve head toward the macula and occurs regardless of the amount of swelling of the rest of the peripapillary fibers.

FASTQ files of proband's WES (whole exome sequencing)

Leber's hereditary optic neuropathy (LHON) is the most frequent mitochondrial disease and was the first to be genetically defined by a point mutation in mitochondrial DNA (mtDNA). A molecular diagnosis is achieved in up to 95% of cases, the vast majority of which are accounted for by 3 mutations within mitochondrial complex I subunit-encoding genes in the mtDNA (mtLHON). Here, we resolve the enigma of LHON in the absence of pathogenic mtDNA mutations. We describe biallelic mutations in a nuclear encoded gene, DNAJC30, in 33 unsolved patients from 29 families and establish an autosomal recessive mode of inheritance for LHON (arLHON), which to date has been a prime example of a maternally inherited disorder. Remarkably, all hallmarks of mtLHON were recapitulated, including incomplete penetrance, male predominance, and significant idebenone responsivity. Moreover, by tracking protein turnover in patient-derived cell lines and a DNAJC30-knockout cellular model, we measured reduced turnover of specific complex I N-module subunits and a resultant impairment of complex I function. These results demonstrate that DNAJC30 is a chaperone protein needed for the efficient exchange of complex I subunits exposed to reactive oxygen species and integral to a mitochondrial complex I repair mechanism, thereby providing the first example to our knowledge of a disease resulting from impaired exchange of assembled respiratory chain subunits.

Purpose Peripapillary hyperreflective ovoid mass-like structures (PHOMS) are novel and not well characterized findings occurring in several disorders of the optic nerve. The aim of this study is to present two cases of tilted disc syndrome (TDS) and one case with optic disc drusen undergoing a multimodal imaging approach. Methods In this case series, a qualitative evaluation of the OCTA findings in regions with PHOMS was performed. Results Structural OCT revealed the presence of PHOMS. OCTA identified the presence of a vascular complex within this hyperreflective structure. Conclusions Assuming that PHOMS are thought to correspond to herniating nerve fibers or be secondary to axoplasmic stasis, this vascular complex may represent a displacement of the deeper vessels deputed at the irroration of the optic nerve into the retina or, alternatively, might be secondary to an increase in vascular endothelial growth factor (VEGF) levels and a subsequent development of neovessels.

Purpose To investigate the relationship between retinal structure and macular function in eyes screened for hydroxychloroquine (HCQ) toxicity. Methods Participants referred for hydroxychloroquine retinopathy screening with spectral domain optical coherence tomography (SD-OCT) and multifocal electroretinogram (mfERG) testing were included in the analysis. Amplitude and implicit time of mfERG N1 and P1 responses were included in the analysis. Ring ratios were computed for amplitude values as the ratio of rings 1–3:5 (R1–3:R5). A control group of healthy participants was included for comparison of SD-OCT metrics. Results Sixty-three eyes screened for HCQ retinopathy and 30 control eyes were analyzed. The outer nuclear layer (ONL) was significantly thinner in HCQ patients in the foveal (P = 0.008), parafoveal (P < 0.0001), and perifoveal (P < 0.0001) regions. The HCQ cohort was further divided into two subgroups according to the presence of structural clinically detectable retinopathy (i.e., structural damage as detected by multimodal imaging). HCQ eyes without retinopathy had a thinner ONL thickness in the foveal (P = 0.032), parafoveal (P < 0.0001), and perifoveal (P < 0.0001) regions and a thinner inner nuclear layer (INL) in the parafoveal region (P = 0.045 versus controls). Structural changes in HCQ patients without retinopathy were significantly associated with macular function as R2:R5 ring ratio of mfERG P1 amplitude was associated with INL (P = 0.002) and ONL (P = 0.044) thicknesses, and R3:R5 ring ratio of P1 amplitude was associated with ONL thickness (P = 0.004). Conclusions Our results suggest that structural alterations secondary to HCQ toxicity may occur in the absence of clinically detectable retinopathy, and this may reflect in an impaired macular function.

Importance: The contribution of the microvascular supply to the pathogenesis of Leber's hereditary optic neuropathy (LHON) is poorly understood. Background: We aimed at measuring the peripapillary capillary vessel density (VD) using optical coherence tomography angiography (OCT-A) at different stages of LHON. Design: Prospective, cross-sectional, multicenter, observational study. Participants: Twenty-two LHON patients divided in four groups: unaffected mutation carriers (LHON-u); early sub-acute stage (LHON-e); late sub-acute stage (LHON-l); chronic stage (LHON-ch). Methods: OCT-A scans centred on the optic disc were obtained by spectral domain OCT system. Main Outcome Measures: VD, retinal nerve fibre layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thickness were compared between groups. Results: Significant VD changes were detected in every sector (P < 0.0001). In LHON-e, the VD was reduced in the temporal sector compared with LHON-u and in the temporal and inferotemporal sectors compared with controls. In LHON-l, VD was reduced in whole, temporal, superotemporal and inferotemporal sectors compared with LHON-u and controls. In LHON-ch, the VD was reduced in all sectors compared to the other groups. An asynchronous pattern emerged in the temporal sector with VD changes occurring earlier than RNFL thickness changes and together with GC-IPL thinning. Conclusions and Relevance: Significant peripapillary miscrovascular changes were detected over the different stages of LHON. Studying the vascular network separately from fibres revealed that microvascular changes in the temporal sector preceded the changes of RNFL and mirrored the GC-IPL changes. Measurements of the peripapillary vascular network may become a useful biomarker to monitor the disease process, evaluate therapeutic efficacy and elucidate pathophysiology.

Purpose: To assess preganglionic retinal function using multifocal electroretinogram (mfERG) in patients affected by dominant optic atrophy (DOA) stratified by OPA1 gene mutation. Methods: Multifocal electroretinogram (mfERG) was recorded in 18 DOA patients (DOA group, 35 eyes) and 25 age-matched healthy subjects (control group, 25 eyes). Patients were stratified in two groups based on gene mutation: missense mutation (DOA-M group, 11 eyes) and mutation causing haploinsufficiency (DOA-H group, 24 eyes). The mfERG N1-P1 response amplitude density (RAD) has been evaluated in five annular retinal areas with different eccentricity from the fovea (ring 1: 0–5 degrees, R1; ring 2: 5–10 degrees, R2; ring 3: 10–15 degrees, R3; ring 4: 15–20 degrees, R4; and ring 5: 20–25 degrees, R5) and in eight sectors on the basis of the retinal topography: temporal–superior (TS), temporal–inferior (TI), nasal–superior (NS) and nasal–inferior (NI), temporal (T), superior (S), nasal (N) and inferior (I). Results: Compared to controls, DOA group revealed a significant reduction in N1-P1 RADs values in R1-R4 rings and in TI, NS and N sectors [analysis of variance (ANOVA), pÂ

Aims: To evaluate changes in macular morphology and function after repeated intravitreal dexamethasone implant (Ozurdex((R))) for macular edema (ME) due to retinal vein occlusion (RVO). Methods: Consecutive treatment-naive patients with ME secondary to RVO were treated with Ozurdex and followed up to 12 months to evaluate functional and morphological outcomes by means of best-corrected visual acuity (BCVA) and microperimetry and by enhanced depth imaging optical coherence tomography, respectively. Results: Thirty-five eyes of 35 patients were included for the analysis (26 central RVO, 9 branch RVO). During the 12-month study period, 8 of the 35 eyes (23%) underwent 1 intravitreal dexamethasone implant, 13 of the 35 eyes (37%) underwent 2, and 14 of the 35 eyes (40%) underwent 3 intravitreal dexamethasone implants. At 1 month from the 1st intravitreal dexamethasone implant, the mean BCVA, retinal sensitivity and central macular thickness (CMT) significantly improved compared to the baseline values. At 3 months, the mean BCVA improvement was no more significant, while retinal sensitivity further improved and CMT slightly worsened, remaining, however, significantly better than at baseline. At 12 months, those eyes that had undergone 2 retreatments showed a significant improvement of the mean BCVA, mean retinal sensitivity and CMT compared to the baseline values [0.61 +/- 0.29 logarithm of the minimum angle of resolution (LogMAR) vs. 0.82 +/- 0.33 LogMAR, p = 0.011; 12.94 +/- 4.73 dB vs. 10.75 +/- 3.27 dB, p = 0.043, and 321 +/- 91 mu m vs. 735 +/- 169 mu m, p = 0.001, respectively]. In those eyes that had undergone only 1 retreatment, a significant improvement was recorded only for the CMT (500 +/- 224 mu m vs. 695 +/- 302 mu m, p = 0.044). The mean retreatment interval between the 1st and the 2nd injection was 4.5 +/- 1.1 months (range 3-7 months), and between the 2nd and the 3rd injection it was 4.1 +/- 1 months (range 3-6 months). Conclusions: In eyes with ME secondary to RVO, Ozurdex produces functional benefits as early as 1 month after treatment/retreatment. Current optical coherence tomography and microperimetry findings confirm the concept that, in most cases, the optimum retreatment interval should be

A 32-year-old man was referred to the authors’ department for nonspecified macular dystrophy with persistent metamorphopsia in the right eye diagnosed 10 years before and followed using optical coherence tomography. The patient underwent a comprehensive ocular examination, including multimodal imaging evaluation and electrofunctional testing. The diagnosis was consistent with nonconforming focal choroid excavation. Over 10 years, no complications occurred, visual acuity was stable, and optical coherence tomography showed no progression of the lesion during follow-up. In this case, nonconforming symptomatic focal choroid excavation was a nonprogressive condition with good long-term visual outcome. [ Ophthalmic Surg Lasers Imaging Retina . 2015;46:125–130.]

Peripapillar and nerve head vessel density (VD) was measured in 10 patients affected by Dominant optic atrophy (DOA) using optical coherence tomography angiography (OCT-A) and compared to the measurements of 15 age- and gender-matched controls. DOA patients showed VD reduction, mostly in the temporal and inferotemporal peripapillary sectors, according to the preferential involvement of the papillomacular bundle. Despite poor best-corrected visual acuity (BCVA), OCT-A revealed good repeatability. VD correlated with functional (mean deviation of visual field and BCVA) and structural (retinal nerve fiber layer thickness) parameters and could be a non-invasive, quantitative tool for the monitoring of the disease and of the therapeutic approaches.

Purpose: To assess the effects of intravitreal bevacizumab injections in the treatment of extrafoveal choroidal neovascularization (CNV) associated with pathologic myopia. Methods: Patients diagnosed with pathologic myopia complicated by extrafoveal CNV were considered in this prospective, open-label interventional study. All patients underwent a complete ophthalmologic examination, including Early Treatment Early of Diabetic Retinopathy Study (ETDRS) visual acuity measurement, optical coherence tomography, and fluorescein angiography. The protocol treatment included a first injection, followed by repeated injections over a 24-month follow-up period on the basis of optical coherence tomography and angiographic features, monitored monthly. Primary outcomes were the mean changes in best-corrected visual acuity and the proportion of eyes gaining at least 15 letters at the 24-month examination. Secondary outcomes included central macular thickness, size of the CNV, and extension to the fovea. Results: Fifteen patients were included in the study. Mean best-corrected visual acuity changed from 0.47 logarithm of the minimum angle of resolution (20/60 Snellen equivalent) at baseline to 0.22 logarithm of the minimum angle of resolution (20/30 Snellen equivalent) at the 24-month examination. An improvement of at least 3 ETDRS lines was achieved by 7 eyes (46.6%) at the 24-month examination. Mean central macular thickness changed from 313 mu m to 254 mu m at the 24-month examination (P = 0.008). Mean CNV size decreased from 348 mu m(2) to 251 mu m(2) at 24 months (P = 0.029). Conclusion: Intravitreal bevacizumab injection is a beneficial treatment for extrafoveal CNV associated with pathologic myopia. RETINA 33:593-597, 2013

Leber’s hereditary optic neuropathy (LHON) is typically characterized by vascular alterations in the acute phase. The aim of this study was to evaluate choroidal changes occurring in asymptomatic, acute and chronic stages of LHON. We enrolled 49 patients with LHON, 19 with Dominant Optic Atrophy (DOA) and 22 healthy controls. Spectral Domain-Optical Coherence Tomography (SD-OCT) scans of macular and peripapillary regions were performed in all subjects, to evaluate macular and peripapillary choroidal thickness, and retinal nerve fiber layer (RNFL) thicknes. Macular and peripapillary choroidal thicknesses were significantly increased in the acute LHON stage. On the contrary, macular choroidal thickness was significantly reduced in the chronic stage. Furthermore, peripapillary choroidal thickness was decreased in chronic LHON and in DOA. Both RNFL and choroid had the same trend (increased thickness, followed by thinning), but RNFL changes preceded those affecting the choroid. In conclusion, our study quantitatively demonstrated the involvement of the choroid in LHON pathology. The increase in choroidal thickness is a feature of the LHON acute stage, which follows the thickening of RNFL. Conversely, thinning of the choroid is the common outcome in chronic LHON and in DOA.

none 12 si AIMS: To evaluate longitudinal retinal ganglion cell inner plexiform layer (GC-IPL) and macular retinal nerve fibre layer (mRNFL) thickness changes in acute Leber's hereditary optic neuropathy (LHON). METHODS: Six eyes of four patients with LHON underwent SD-OCT (optical coherence tomography) at month 1, 3, 6 and 12 after visual loss. In two eyes, the examination was carried out in the presymptomatic stage. The relationship and curves for area under the receiver operator characteristic (AUROC) were generated to assess the ability of each parameter to detect ganglion cell loss. RESULTS: Significant longitudinal thinning of GC-IPL and mRNFL was detected in LHON. GC-IPL thinning was detectable in the deviation map during the presymptomatic stage in the inner ring of the nasal sector and then it progressively extended following a centrifugal and spiral pattern. Similarly, mRNFL thinning began in the inferonasal sector and it progressively extended. No further statistically significant changes were detected after month 3. The highest level of AUROC values at 1 month were detected in the nasal sectors and inferonasal mRNFL thickness reached AUROC value=1. All the parameters were equally able to detect ganglion cell loss from month 2 to 12. CONCLUSIONS: The natural history of GC-IPL thinning follows a specific pattern of reduction, reflecting the anatomical course of papillomacular fibres. Month 6 represents the end of GC-IPL loss. GC-IPL and mRNFL thinning is detectable before onset of visual loss. These observations can help future therapeutic approaches for both LHON carriers at high risk of conversion and patients with acute early LHON. Fondazione Bietti is supported by the Italian Ministry of Health and Fondazione Roma; IRCCS Istituto di Scienze Neurologiche di Bologna is supported by the Ministry of Health. mixed Balducci, Nicole; Savini, Giacomo; Cascavilla, Maria Lucia; La Morgia, Chiara; Triolo, Giacinto; Giglio, Rosa; Carbonelli, Michele; Parisi, Vincenzo; Sadun, Alfredo A; Bandello, Francesco; Carelli, Valerio; Barboni, Piero Balducci, Nicole; Savini, Giacomo; Cascavilla, Maria Lucia; La Morgia, Chiara; Triolo, Giacinto; Giglio, Rosa; Carbonelli, Michele; Parisi, Vincenzo; Sadun, Alfredo A; Bandello, Francesco; Carelli, Valerio; Barboni, Piero

Purpose: To compare intravitreal bevacizumab (IVB) and intravitreal ranibizumab (IVR) in the treatment of subfoveal choroidal neovascularization associated with pathologic myopia. Methods: Fifty-five patients fulfilling inclusion and exclusion criteria were randomized either to IVB or to IVR. After the first injection, re-treatments were performed on a pro re nata basis in monthly examinations over an 18-month follow-up. Primary outcome measures were the change in mean best-corrected visual acuity and the proportion of eyes improving in best-corrected visual acuity by > 1 and > 3 lines at the 18-month examination. Results: Forty-eight eyes received the treatment and were subsequently included in the analysis. At the 18-month examination, a significant improvement of 1.7 lines and 1.8 lines compared with baseline were noticed in the IVR and IVB subgroups, respectively. The difference in the final mean best-corrected visual acuity between the groups was not significant. A 3-line gain or higher was noted in 30% of eyes in the IVR subgroup and 44% of eyes in the IVB subgroup. Although both groups attained a significant improvement in central macular thickness, the IVR subgroup achieved a faster central macular thickness reduction. A significantly lower number of injections were administered in the IVR subgroup (2.5) compared with the IVB subgroup (4.7; P < 0.001). Conclusion: Intravitreal ranibizumab and IVB are effective in the treatment of subfoveal myopic choroidal neovascularization. Intravitreal ranibizumab achieved greater efficacy than IVB in terms of the mean number of injections administered. RETINA 32:1539-1546, 2012

Purpose TO report a case of retinopathy secondary to malignant hypertension showing a macular star, which responded favorably to a single intravitreal injection of bevacizumab (IVB). Methods A 46-year-old man with malignant hypertension showing incomplete macular star in his right eye with best-corrected visual acuity (BCVA) of 20/32 underwent IVB. Results Subsequent examinations revealed a progressive resolution of the macular star with functional recovery over the follow-up. In particular, at the 9-month examination BCVA was 20/20, fundus biomicroscopy disclosed resolution of the macular star, and the retinal sensitivity improved remarkably. Conclusions Intravitreal injection of bevacizumab can be a useful approach to treat the exudative manifestations of malignant hypertension.

Purpose: To evaluate the rate of adherence to prescribed nutritional supplementation in patients affected by age-related macular degeneration, in an Italian tertiary referral tertiary center. Methods: Patients with age-related macular degeneration, age-related eye disease study Categories 3 and 4, were recruited and underwent an 11-item questionnaire. Results: The study included a total of 193 patients meeting the age-related eye disease study nutritional supplementation criteria (174 patients with age-related eye disease study Category 4 and 19 with Category 3). Seventy-seven (40%) were taking oral supplementation, 70 of whom (90%) 1 tablet/day. Oral supplementation was recommended by the personal ophthalmologist in 85 patients (44%), including all those currently receiving it. Eight patients of 85 (9.4%) rejected supplementation despite it being recommended, mostly because they were already taking other medicines. Ninety-four patients (48%) claimed they had not received any information from their ophthalmologist. Conclusion: Our data reveal that Italian patients with age-related eye disease study Categories 3 and 4 have a low adherence to nutritional supplementation. In 65% of cases, patients were not adequately informed by their ophthalmologist of the potential benefits of oral supplementation for age-related macular degeneration; indeed, 108 patients (56%) were not even aware such nutritional treatments are available. Ophthalmologists should be aware of the importance of giving advice to persons with age-related macular degeneration regarding the benefits of oral supplements.

Author(s): Carbonelli, Michele; La Morgia, Chiara; Savini, Giacomo; Cascavilla, Maria Lucia; Borrelli, Enrico; Chicani, Filipe; do V F Ramos, Carolina; Salomao, Solange R; Parisi, Vincenzo; Sebag, Jerry; Bandello, Francesco; Sadun, Alfredo A; Carelli, Valerio; Barboni, Piero | Abstract: PurposeTo investigate the thickness of the retinal layers and to assess the prevalence of macular microcysts (MM) in the inner nuclear layer (INL) of patients with mitochondrial optic neuropathies (MON).MethodsAll patients with molecularly confirmed MON, i.e. Leber's Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA), referred between 2010 and 2012 were enrolled. Eight patients with MM were compared with two control groups: MON patients without MM matched by age, peripapillary retinal nerve fiber layer (RNFL) thickness, and visual acuity, as well as age-matched controls. Retinal segmentation was performed using specific Optical coherence tomography (OCT) software (Carl Zeiss Meditec). Macular segmentation thickness values of the three groups were compared by one-way analysis of variance with Bonferroni post hoc corrections.ResultsMM were identified in 5/90 (5.6%) patients with LHON and 3/58 (5.2%) with DOA. The INL was thicker in patients with MON compared to controls regardless of the presence of MM [133.1±7μm vs 122.3±9μm in MM patients (pl0.01) and 128.5±8μm vs. 122.3±9μm in no-MM patients (pl0.05)], however the outer nuclear layer (ONL) was thicker in patients with MM (101.4±1mμ) compared to patients without MM [77.5±8mμ (pl0.001)] and controls [78.4±7mμ (pl0.001)]. ONL thickness did not significantly differ between patients without MM and controls.ConclusionThe prevalence of MM in MON is low (5-6%), but associated with ONL thickening. We speculate that in MON patients with MM, vitreo-retinal traction contributes to the thickening of ONL as well as to the production of cystic spaces.

Purpose:To compare retinal sensitivity obtained with MP1 and MAIA microperimeters in patients affected by retinal dystrophies (RD) and in healthy subjects.Methods:Thirty-six patients affected by RD and 25 healthy subjects were considered for the study. All patients and controls underwent a complete ophthalmic examination including fundus-related perimetry, performed by means of two microperimeters, the MP1 (Nidek Technologies) and the MAIA (CenterVue). Main outcome of the study was the comparison of retinal sensitivity. Such comparison was performed converting the MP1 decibel (dB) values to their MAIA equivalent dB values.Results:Mean retinal sensitivity in patients affected by RD was 5.68 6.08 dB (mean +/- SD) on MP1 (9.66 +/- 10.06 dB converted to their equivalent MAIA values) and 14.66 +/- 9.37 dB on MAIA (P < 0.0001). Mean retinal sensitivity in healthy subjects was 18.46 +/- 3.10 dB on MP1 (22.44 +/- 7.08 dB on their converted equivalent MAIA values) and 28.52 +/- 1.12 dB on MAIA (P < 0.0001). Thirty eyes affected by RD (41%) showed retinal areas characterized by sensitivity under 1 dB on MP1, whereas the MAIA examination of the same areas revealed a mean retinal sensitivity of 4.7 dB. Moreover, 28 of these eyes disclosed also areas of absolute scotoma on MP1, but examining the same areas on MAIA, just 13 of these eyes (46%) disclosed an absolute scotoma. In addition, in a subgroup of 6 eyes affected by RD (8%) showing a retinal sensitivity of 20 dB on MP1, the corresponding value on MAIA varied from 26.3 dB to 30.0 dB, with a mean value of 27.8 +/- 1.3 dB.Conclusion:The MAIA microperimeter provides a more accurate characterization of functional impairment in RD with respect to the MP1 system, especially in cases with low and high retinal sensitivity. MAIA microperimeter could reveal particularly useful in precisely identifying and monitoring subtle changes in retinal sensitivity, especially in view of the availability of therapies aiming at a functional rescue in patients with RD.

Using advanced MRI techniques, we investigated the presence and topographical distribution of brain grey matter (GM) and white matter (WM) alterations in dominant optic atrophy (DOA) patients with genetically proven OPA1 mutation as well as their correlation with clinical and neuro-ophthalmologic findings. Nineteen DOA patients underwent neurological, neuro-ophthalmologic and brainstem auditory evoked potentials (BAEP) evaluations. Voxel-wise methods were applied to assess regional GM and WM abnormalities in patients compared to 20 healthy controls. Visual acuity was reduced in 16 patients. Six DOA patients (4 with missense mutations) had an abnormal I peripheral component (auditory nerve) at BAEP. Compared to controls, DOA patients had significant atrophy of the optic nerves (p < 0.0001). Voxel-based morphometry (VBM) analysis showed that, compared to controls, DOA patients had significant WM atrophy of the chiasm and optic tracts; whereas no areas of GM atrophy were found. Tract-based spatial statistics (TBSS) analysis showed that compared to controls, DOA patients had significantly lower mean diffusivity, axial and radial diffusivity in the WM of the cerebellum, brainstem, thalamus, fronto-occipital-temporal lobes, including the cingulum, corpus callosum, corticospinal tract and optic radiation bilaterally. No abnormalities of fractional anisotropy were detected. No correlations were found between volumetric and diffusivity abnormalities quantified with MRI and clinical and neuro-ophthalmologic measures of disease severity. Consistently with pathological studies, tissue loss in DOA patients is limited to anterior optic pathways reflecting retinal ganglion cell degeneration. Distributed abnormalities of diffusivity indexes might reflect abnormal intracellular mitochondrial morphology as well as alteration of protein levels due to OPA1 mutations.

Purpose Retinal dystrophies show a considerably wide phenotypic variability which can make the diagnosis and the clinical staging difficult. Aim of the study is to analyze the contribution of retro-mode imaging (RMI) and fundus autofluorescence to the characterization and the staging of the retinal dystrophies. Methods Eighteen patients affected by retinal dystrophies (2 patients with Best Vitelliform Macular Dystrophy (BVMD), 5 patients with autosomal recessive Stargardt Disease-Fundus Flavimaculatus (STGD1), 8 patients with Pattern Dystrophy, 2 patients with Choroideremia (CHM), and 1 patient with Benign Concentric Annular Macular Dystrophy (BCAMD) were recruited for the study. All the patients underwent a complete ophthalmological examination, including best corrected visual acuity with ETDRS charts, blue-light autofluorescence, (BL-AF), near-infrared autofluorescence (NI-AF), and RMI. Results Overall, the main feature of RMI is represented by a pseudo-3D pattern of all the lesions at the posterior pole. More specifically, any accumulation of material within the retina appear as an area of elevation with different shape and sizes, showing irregular and darker borders. BL-AF reveals the deposition of lipofuscin, whereas NIR-AF shows alterations in the melanin distribution. Conclusions There is no precise correlation among RMI, BL-AF, and NIR-AF imaging. RMI and fundus autofluorescence appear as useful tools for the identification and follow-up of retinal dystrophies. Non-invasive diagnostic tools may yield additional information in the clinical setting and the monitoring of the patients.

Purpose Melanin is a protective agent from light and oxidative damages. Melanin distribution can be visualized by means of near-infrared fundus autofluorescence (NIR-FAF). Aim of the study is to describe the NIR-FAF patterns in early stages of age-related macular degeneration (AMD) and to compare them with the patterns visible with blue-light fundudautofluorescence (BL-FAF). Methods Eighty-four patients affected by age-related maculopathy were considered for the study. Each patient underwent a complete ophthalmologic examination including EDTRS best corrected visual acuity (BCVA), NIR-FAF, and BL-FAF. The results were compared with those obtained in 40 health, age-matched subjects. Results Four NIR-FAF patterns were identified. More specifically, normal pattern was detected in 7%, normal pattern associated with hyper/hypoautofluorescent spot not involving the fovea was identified in 65.5%. Moreover, normal pattern associated with hyper/hypoautofluorescent spot involving the fovea, and patchy pattern were visible in 15.5% and 12% of cases, respectively. Minimal change and focal increased were the most frequent patterns detectable on BL-FAF. Lower BCVA value was associated with foveal involvement. Conclusions NIR-FAF shows specific patterns in early stages of AMD. There is no direct correlation between BL-FAF and NIR-FAF patterns. BL-FAF turned out to be altered in all cases, whereas NIR-FAF was normal in 7% of cases. Central involvement on NIR-FAF corresponded to lower BCVA.

Purpose Dome-shaped macula (DSM) has been described recently as an inward convexity of the macula typical of myopic eyes detectable on spectral-domain optical coherence tomography (SD-OCT). The authors describe a case of monolateral DSM associated with Best vitelliform macular dystrophy (VMD). Methods Case report. Results A 60-year-old man already diagnosed with VMD in vitelliruptive stage underwent SD-OCT that revealed the typical vitelliform material accumulation associated in the left eye with a convex elevation of the macula. No change was registered over a 1-year follow-up. Conclusions This is the first report describing a monolateral DSM associated with VMD. Dome-shaped macula could be considered as a nonspecific scleral alteration, probably due to increased scleral thickness, which can accompany many retinal disorders.

Purpose. To investigate changes in macular function after intravitreal dexamethasone implant (Ozurdex) for macular edema (ME) secondary to retinal vein occlusion (RVO). Methods. Nineteen treatment-naive patients with RVO-related ME were treated with intravitreal Ozurdex and followed up to 6 months to evaluate functional outcomes, by means of best-corrected visual acuity, microperimetry, and multifocal electroretinography, and their correlations with morphological parameters by enhanced depth imaging optical coherence tomography. Results. Nineteen eyes of 19 patients were included for analysis. At 1 month, mean best-corrected visual acuity, retinal sensitivity, and central macular thickness (CMT) improved from 0.50 +/- 0.34 LogMAR, 10.51 +/- 4.31 dB, and 762 +/- 259 mu m (baseline) to 0.38 +/- 0.34 LogMAR (p = 0.043), 12.28 +/- 5.06 dB (p = 0.025), and 385 +/- 191 mu m (p = 0.001), respectively. At 3 months, improvement of mean retinal sensitivity and CMT was still significant (11.62 +/- 5.05 dB [p = 0.047] and 518 +/- 251 mu m [p = 0.006]). Multifocal electroretinography measurements also showed (nonsignificant) improvement. No significant changes in choroidal thickness were recorded. Improvements recorded during the first 3 months were no longer significant from month 4. At each time point, we found a negative significant correlation between CMT and retinal sensitivity. Interestingly, 7 eyes did not undergo retreatment of less than 6 months; these eyes showed a significantly better baseline retinal sensitivity than eyes requiring retreatment of less than 6 months (12.27 +/- 3.52 dB vs. 9.48 +/- 4.53 dB [p = 0.038]). Conclusions. In eyes with ME secondary to RVO, intravitreal dexamethasone implant provides functional benefits as soon as 1 month after treatment. In most cases, the optimum retreatment interval is less than 6 months from first intravitreal Ozurdex. Microperimetry is a very useful tool to characterize macular function. Baseline macular sensitivity may predict the need for early (

Acute macular neuroretinopathy (AMNR) is a rare retinal disorder characterized by the occurrence of wedge-shaped lesions localized at the macular region, and resulting in unilateral or bilateral macular scotomata. Although the etiology is not completely defined, vascular alterations are thought to play a possible role in the origin of morphological changes involving the outer retina. In the current study, we describe the anatomical findings associated with acute macular neuroretinopathy evaluated by mean of spectral domain-OCT and the clinical contribution of the ‘en face' SD-OCT to monitoring of the retinal changes over the follow-up.

PURPOSE: To assess the peripapillary retinal nerve fiber and macular retinal ganglion cell (RGC) loss in patients with dominant optic atrophy (DOA) stratified by OPA1 mutation type. DESIGN: Cross-sectional study. METHODS: We studied 39 patients from 28 pedigrees with DOA harboring heterozygous mutations in the OPA1 gene along with 45 age-matched healthy subjects. The retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) of patients with DOA were evaluated by optical coherence tomography (OCT) and compared to those of controls. Patients' eyes were divided into 4 groups based on increasing severity of visual loss (DOA1 to DOA4) and were stratified by OPA1 mutation type. RESULTS: The average thicknesses of the RNFL and GC-IPL were smaller in patients with DOA than in healthy controls (P < 0.0001). RNFL analysis showed a significant reduction of the average, superior and inferior quadrants thicknesses in the DOA4 group compared to the DOA1 group (P = 0.001, P = 0.002 and P = 0.001, respectively). GC-IPL analysis showed a significant thinning in the superotemporal and superior sectors in the patients with DOA2 compared to those with DOA1 (P = 0.046 and P = 0.04, respectively). Stratifying by mutation type, average, superior and nasal RNFL thinning was significantly more severe in missense mutations and had a presumed dominant-negative effect compared to mutations causing haploinsufficiency. CONCLUSIONS: The present study demonstrates that in DOA, loss of macular RGCs is the earliest pathologic event, better reflected by GC-IPL measurements, whereas RNFL thickness is a measure of spared axons in late stages of the disease. Thus, mild cases (DOA2) show significant macular RGC loss as opposed to substantial maintenance of RNFL thickness, which is significantly decreased only in severe cases (DOA4). A clear genotype/phenotype correlation emerged, stratifying OCT measures by OPA1 mutation type, missense mutations being the most severe. (C) 2014 by Elsevier Inc. All rights reserved.

Purpose: To investigate the impact of intravitreal dexamethasone implant (Ozurdex) on macular morphology and function in eyes with macular edema secondary to central retinal vein occlusion. Methods: Twelve treatment-naive patients with decreased visual acuity because of central retinal vein occlusion-related macular edema were enrolled in this prospective uncontrolled study. Patients were treated with intravitreal Ozurdex and followed up at 1 month and 3 months for the evaluation of morphologic and functional outcomes, by means of best-corrected visual acuity, microperimetry, multifocal electroretinography, and customized high-resolution enhanced depth imaging spectral-domain optical coherence tomography scans. Results: Twelve eyes of 12 patients (10 men, 2 women; mean age 56.2 +/- 13.0 years) were included for analysis. At 1 month, mean best-corrected visual acuity, retinal sensitivity (microperimetry), multifocal electroretinography parameters, central macular thickness, and specific neurosensorial retinal measurements improved significantly. We found a significant negative correlation between retinal sensitivity and central macular thickness at 1 month and 3 months (r = -0.831, P = 0.001; r = -0.881, P = 0.001; respectively). Moreover, retinal sensitivity was negatively related to both outer and inner retinal thickness in all four intervals from the fovea. From baseline to Month 1, change in outer retinal thickness was positively related to multifocal electroretinography N1R1 amplitude change (r = 0.698, P = 0.012), whereas change in central macular thickness was negatively related to multifocal electroretinography P1R1 amplitude change (r = -0.701, P = 0.011). At 3 months, improvement of mean retinal sensitivity and central macular thickness slightly decreased. Conclusion: In eyes with macular edema secondary to central retinal vein occlusion, intravitreal dexamethasone provides functional benefits that correlate well with ultrastructural macular changes. Purpose: To investigate the impact of intravitreal dexamethasone implant (Ozurdex) on macular morphology and function in eyes with macular edema secondary to central retinal vein occlusion. Methods: Twelve treatment-naive patients with decreased visual acuity because of central retinal vein occlusion-related macular edema were enrolled in this prospective uncontrolled study. Patients were treated with intravitreal Ozurdex and followed up at 1 month and 3 months for the evaluation of morphologic and functional outcomes, by means of best-corrected visual acuity, microperimetry, multifocal electroretinography, and customized high-resolution enhanced depth imaging spectral-domain optical coherence tomography scans. Results: Twelve eyes of 12 patients (10 men, 2 women; mean age 56.2 +/- 13.0 years) were included for analysis. At 1 month, mean best-corrected visual acuity, retinal sensitivity (microperimetry), multifocal electroretinography parameters, central macular thickness, and specific neurosensorial retinal measurements improved significantly. We found a significant negative correlation between retinal sensitivity and central macular thickness at 1 month and 3 months (r = -0.831, P = 0.001; r = -0.881, P = 0.001; respectively). Moreover, retinal sensitivity was negatively related to both outer and inner retinal thickness in all four intervals from the fovea. From baseline to Month 1, change in outer retinal thickness was positively related to multifocal electroretinography N1R1 amplitude change (r = 0.698, P = 0.012), whereas change in central macular thickness was negatively related to multifocal electroretinography P1R1 amplitude change (r = -0.701, P = 0.011). At 3 months, improvement of mean retinal sensitivity and central macular thickness slightly decreased. Conclusion: In eyes with macular edema secondary to central retinal vein occlusion, intravitreal dexamethasone provides functional benefits that correlate well with ultrastructural macular changes.

Aim: To evaluate the agreement between fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT) in detecting myopic choroidal neovascularization (CNV) activity during bevacizumab treatment. Methods: Thirty-four patients with subfoveal myopic CNV were prospectively enrolled. FA and SD-OCT were performed at baseline and at all planned monthly visits. After the first injection, additional treatments were administered following detection of fluid on SD-OCT and/or leakage on FA. κ-Analysis was performed to examine the agreement between FA and SD-OCT. Results: At baseline, FA and SD-OCT agreed in 26/34 cases (κ = 0.23); sensitivity and specificity were 77.4 and 66.7%, respectively. Seven eyes presented leakage on FA with no fluid on SD-OCT, 1 case showed intraretinal fluid on SD-OCT and no leakage on FA. At the 1-month examination, specificity and κ-value improved, and 30/34 cases showed complete concordance. At the 3- and 4-month examinations, a discordance was noted in 6 cases. From the 5-month examination on, a correspondence was achieved in at least 30/34 cases and reached a perfect match in 11 sessions. Conclusions: Our study confirms the key role of FA in diagnosing myopic CNV. It seems possible there may be a role for SD-OCT in assisting FA to monitor the myopic CNV activity during anti-vascular endothelial growth factor antibody treatment.

Purpose To report on intravitreal Ranibizumab for intervening myopic choroidal neovascularization (CNV) in a case of retinal detachment successfully repaired with pars plana vitrectomy and silicone oil tamponade. Methods Intravitreal ranibizumab was performed in a 67-year-old woman with CNV complicating pathologic myopia. The patient had previously undergone vitrectomy and silicone oil tamponade for retinal detachment. Results At 2 months from intravitreal ranibizumab, best-corrected visual acuity (BCVA) improved from count fingers to 20/100, and intraocular pressure (IOP) was 16 mm Hg. Fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT) showed resolution of late leakage and subretinal/intraretinal fluid, respectively. Conclusions Administration of intravitreal anti-V EGF in patients with silicone oil as intraocular tamponade may represent an intriguing treatment option. Our results suggest that intravitreal injections of Ranibizumab may lead to a rapid improvement in both functional (BCVA) and morphologic (FA and SD-OCT) parameters of CNV activity, without significant rise in IOP, in eyes with silicone oil as intraocular tamponade.

Purpose: To evaluate the effects of repeated intravitreal dexamethasone implant (IDI) (Ozurdex (R)) in eyes with macular edema (ME) due to retinal vein occlusion (RVO). Methods: We reviewed the charts of patients with RVO-related ME, who received repeated Ozurdex IDI (0.7 mg) on an 'as-needed' basis. Main outcome measures included changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), retreatment interval, and incidence of side effects. Results: A total of 33 eyes were included for analysis. Retreatment with Ozurdex was judged necessary after 4.7 +/- 1.1 months from the first IDI (1st IDI) and 5.1 +/- 1.5 months from the second IDI (2nd IDI). Baseline BCVA was 0.65 +/- 0.43 logMAR; it significantly improved to 0.50 +/- 0.42 logMAR after 1.4 +/- 0.7 months from the 1st IDI (peaking efficacy) (p < 0.001) and to 0.48 +/- 0.44 logMAR after 1.8 +/- 0.8 months from the 2nd IDI (peaking efficacy) (p < 0.001). CMT decreased from 636 +/- 217 mu m (baseline) to 300 +/- 114 mu m, 1.4 +/- 0.7 months after the 1st IDI (p < 0.001), and to 298 +/- 91 mu m, 1.8 +/- 0.8 months after the 2nd IDI (p < 0.001). A rebound effect was recorded in 7 eyes after the 1st IDI (mean 168 +/- 158 mu m) and in 4 eyes after the 2nd IDI (mean 215 +/- 199 mu m). All eyes with a rebound effect improved again after a 2nd intravitreal Ozurdex injection. No serious adverse events were observed; 12 eyes developed a transient IOP increase, and cataracts were extracted in 2 eyes. Conclusion: Repeated intravitreal Ozurdex on an 'as-needed' basis, with a retreatment interval

We report on a 36-year-old man who developed photic maculopathy in the left eye shortly after uncomplicated cataract surgery. The visual acuity (VA) of the left eye was 6/39 and spectral domain optical coherence tomography (SD-OCT), performed one week after surgery, revealed a hyporeflective space in the outer retina (a partial-thickness hole') at the fovea. Microperimetry showed a relative central scotoma and multifocal electroretinogram (ERG) showed reduced responses within the central 10 degrees. Two months later, VA in the felt eye improved to 6/6 and SD-OCT showed an almost complete resolution of the partial-thickness hole'. Microperimetry showed the resolution of the relative scotoma at the fovea and multifocal ERG showed improved responses within the central 10 degrees. SD-OCT, microperimetry and multifocal ERG are useful tools in the diagnosis and follow-up of photic maculopathy after uncomplicated cataract surgery. Its natural history may be characterised by resolution of both morphological and functional changes shortly after surgery. We report on a 36-year-old man who developed photic maculopathy in the left eye shortly after uncomplicated cataract surgery. The visual acuity (VA) of the left eye was 6/39 and spectral domain optical coherence tomography (SD-OCT), performed one week after surgery, revealed a hyporeflective space in the outer retina (a partial-thickness hole') at the fovea. Microperimetry showed a relative central scotoma and multifocal electroretinogram (ERG) showed reduced responses within the central 10 degrees. Two months later, VA in the felt eye improved to 6/6 and SD-OCT showed an almost complete resolution of the partial-thickness hole'. Microperimetry showed the resolution of the relative scotoma at the fovea and multifocal ERG showed improved responses within the central 10 degrees. SD-OCT, microperimetry and multifocal ERG are useful tools in the diagnosis and follow-up of photic maculopathy after uncomplicated cataract surgery. Its natural history may be characterised by resolution of both morphological and functional changes shortly after surgery.

Purpose: To evaluate the effects of a single injection of Ozurdex over 6 months in eyes with persistent diabetic macular edema (DME). Methods: In this retrospective interventional study, 9 patients with decreased visual acuity, as a result of persistent DME, received Ozurdex (intravitreal dexamethasone implant 0.7 mg). Main outcome measures included changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Results: Nine eyes of 9 patients (5 males, 4 females; mean age 58 years) were included in the analysis. The mean duration of DME was 49.9 months (range 24-85). All patients had undergone previous treatments for DME (intravitreal injection of anti-vascular endothelial growth factor, steroids or laser photocoagulation) before entering the study. At baseline, the mean BCVA was 0.74 +/- 0.33 logMAR, and the mean CRT was 502 +/- 222.16 mu m. The mean BCVA was unchanged on the third day (0.74 +/- 0.38 logMAR, p = 0.5), improved to 0.62 +/- 0.32 logMAR (p = 0.02), 0.59 +/- 0.26 logMAR (p = 0.02) and 0.63 8 0.38 logMAR (p = 0.6) after the first, third and fourth months, respectively, and decreased again to 0.73 +/- 0.35 logMAR (p = 0.4) at 6 months. The mean CRT improved to 397 +/- 115.31 mu m (p = 0.17), 271 +/- 99.97 mu m (p = 0.007), 325 +/- 133.05 mu m (p = 0.03) and 462 +/- 176.48 mu m (p = 0.36) on the third day and after 1, 3 and 4 months of follow-up and then increased again to 537 +/- 265.42 mu m (p = 0.33) at 6 months. Eight patients needed retreatments in the sixth month. One eye developed a transient intraocular pressure (IOP) increase 1 month after injection, which was successfully managed with topical IOP-lowering medication. Conclusion: In eyes with persistent DME, Ozurdex produces improvement in BCVA and CRT as soon as the first days after the injection. Such improvement is maintained until the fourth month. Copyright (C) 2012 S. Karger AG, Basel Purpose: To evaluate the effects of a single injection of Ozurdex over 6 months in eyes with persistent diabetic macular edema (DME). Methods: In this retrospective interventional study, 9 patients with decreased visual acuity, as a result of persistent DME, received Ozurdex (intravitreal dexamethasone implant 0.7 mg). Main outcome measures included changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Results: Nine eyes of 9 patients (5 males, 4 females; mean age 58 years) were included in the analysis. The mean duration of DME was 49.9 months (range 24-85). All patients had undergone previous treatments for DME (intravitreal injection of anti-vascular endothelial growth factor, steroids or laser photocoagulation) before entering the study. At baseline, the mean BCVA was 0.74 +/- 0.33 logMAR, and the mean CRT was 502 +/- 222.16 mu m. The mean BCVA was unchanged on the third day (0.74 +/- 0.38 logMAR, p = 0.5), improved to 0.62 +/- 0.32 logMAR (p = 0.02), 0.59 +/- 0.26 logMAR (p = 0.02) and 0.63 8 0.38 logMAR (p = 0.6) after the first, third and fourth months, respectively, and decreased again to 0.73 +/- 0.35 logMAR (p = 0.4) at 6 months. The mean CRT improved to 397 +/- 115.31 mu m (p = 0.17), 271 +/- 99.97 mu m (p = 0.007), 325 +/- 133.05 mu m (p = 0.03) and 462 +/- 176.48 mu m (p = 0.36) on the third day and after 1, 3 and 4 months of follow-up and then increased again to 537 +/- 265.42 mu m (p = 0.33) at 6 months. Eight patients needed retreatments in the sixth month. One eye developed a transient intraocular pressure (IOP) increase 1 month after injection, which was successfully managed with topical IOP-lowering medication. Conclusion: In eyes with persistent DME, Ozurdex produces improvement in BCVA and CRT as soon as the first days after the injection. Such improvement is maintained until the fourth month. Copyright (C) 2012 S. Karger AG, Basel

Aims: It was the aim of this study to report on a patient in whom a novel mutation in the BEST1 gene was responsible for unilateral vitelliform phenotype in autosomal recessive bestrophinopathy (ARB). Methods: An 8-year-old young girl (proband) with unilateral vitelliform phenotype underwent a complete ophthalmologic examination at baseline (time of diagnosis) and 2 years later. Genomic DNA was extracted to look for BEST1 gene mutations in the patient and her parents. Results: Fundus autofluorescence imaging and spectral-domain optical coherence tomography showed unchanged findings in the right eye over the 2-year follow-up period. Conversely, both fundus autofluorescence imaging and spectral-domain optical coherence tomography showed a partial reabsorption of the hyper-autofluorescent/hyper-reflective subretinal material in the left macula over the 2-year follow-up period. On BEST1 gene analysis, the patient presented a novel mutation c.535_537delAAC (p.Asn179del) in homozygous condition; interestingly, despite the absence of parents' consanguinity, both the father and mother showed the same novel mutation in heterozygous condition. Conclusion: This case of unilateral vitelliform phenotype further supports the notion that ARB represents a disease spectrum in terms of severity, age at onset and heritability. Copyright (C) 2012 S. Karger AG, Basel Aims: It was the aim of this study to report on a patient in whom a novel mutation in the BEST1 gene was responsible for unilateral vitelliform phenotype in autosomal recessive bestrophinopathy (ARB). Methods: An 8-year-old young girl (proband) with unilateral vitelliform phenotype underwent a complete ophthalmologic examination at baseline (time of diagnosis) and 2 years later. Genomic DNA was extracted to look for BEST1 gene mutations in the patient and her parents. Results: Fundus autofluorescence imaging and spectral-domain optical coherence tomography showed unchanged findings in the right eye over the 2-year follow-up period. Conversely, both fundus autofluorescence imaging and spectral-domain optical coherence tomography showed a partial reabsorption of the hyper-autofluorescent/hyper-reflective subretinal material in the left macula over the 2-year follow-up period. On BEST1 gene analysis, the patient presented a novel mutation c.535_537delAAC (p.Asn179del) in homozygous condition; interestingly, despite the absence of parents' consanguinity, both the father and mother showed the same novel mutation in heterozygous condition. Conclusion: This case of unilateral vitelliform phenotype further supports the notion that ARB represents a disease spectrum in terms of severity, age at onset and heritability. Copyright (C) 2012 S. Karger AG, Basel

Purpose To describe a rare adverse event characterized by anterior ischemic optic neuropathy (AION) associated with central retinal artery occlusion (CRAO) followed by central retinal vein occlusion (CRVO) secondary to treatment with intravitreal injection of ranibizumab for diabetic macular edema (DME). Methods A patient with DME refractory to focal grid laser photocoagulation in the left eye was prospectively followed and treated with intravitreal injection of ranibizumab. Over a 12-month period and after 4 injections, best-corrected visual acuity (BCVA) improved from 20/63 to 20/50 (Snellen equivalent) and central retinal thickness (CRT) reduced from 551 to 279 μm. In July 2009, BCVA dropped to 20/100 with CRT of 421 μm due to the recurrence of DME and a further injection was administered. Results One month later, the left eye showed a sudden visual acuity loss. Best-corrected visual acuity was 20/400 and the fundus examination revealed a hyperemic and swollen optic disc, with several retinal hemorrhages. Retina at the posterior pole was pale, with attenuation and sheathing of arterial vessels. Fluorescein angiography showed a delayed optic disc and arterial filling with retinal ischemia involving both posterior pole and periphery and confirmed the diagnosis of AION associated with CRAO. One month later, the BCVA decreased to 20/800, and fundus examination evidenced a CRVO with diffuse retinal hemorrhages in the 4 quadrants, congestion, and tortuosity of the retinal veins. Conclusions Although severe ocular adverse events are generally rare, patients receiving intraocular anti-vascular endothelial growth factor injection should be monitored carefully for the development of vascular complications.

Diabetic macular edema is the major cause of visual acuity impairment in diabetic patients. The exact etiopathogenesis is unknown and, currently, grid/focal retinal laser photocoagulation represents the recommended treatment. It has been demonstrated that vascular endothelial growth factor (VEGF) plays a key role in the pathogenesis of diabetic macular edema by mediating vascular permeability and accumulation of intracellular and extracellular fluid, and thereby represents an appealing candidate as a therapeutic target for the treatment of diabetic macular edema. The advent of intravitreal anti-VEGF drugs has opened up a new era for the management of diabetic macular edema. At present, three anti-VEGF substances are available for routine clinical use, ie, pegaptanib, ranibizumab, and bevacizumab. The aim of this review is to summarize the evidence supporting the use of ranibizumab in clinical practice. Most of the studies analyzed in this review are prospective, controlled clinical trials that have focused on documenting the therapeutic effect of ranibizumab and its safety, providing encouraging results.