Ischemic optic neuropathy as first presentation in patient with m.3243 A > G MELAS classic mutation.

BACKGROUND: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a systemic disorder in which multi-organ dysfunction may occur from mitochondrial metabolism failure. Maternally inherited mutations in the MT-TL1 gene are the most frequent causes for this disorder. Clinical manifestations may include stroke-like episodes, epilepsy, dementia, headache and myopathy. Among these, acute visual failure, usually in association with cortical blindness, can occur because of stroke-like episodes affecting the occipital cortex or the visual pathways. Vision loss due to optic neuropathy is otherwise considered a typical manifestation of other mitochondrial diseases such as Leber hereditary optic neuropathy (LHON). CASE PRESENTATION: Here we describe a 55-year-old woman, sister of a previously described patient with MELAS harbouring the m.3243A > G (p.0, MT-TL1) mutation, with otherwise unremarkable medical history, that presented with subacute, painful visual impairment of one eye, accompanied by proximal muscular pain and headache. Over the next weeks, she developed severe and progressive vision loss limited to one eye. Ocular examination confirmed unilateral swelling of the optic nerve head; fluorescein angiography showed segmental perfusion delay in the optic disc and papillary leakage. Neuroimaging, blood and CSF examination and temporal artery biopsy ruled out neuroinflammatory disorders and giant cell arteritis (GCA). Mitochondrial sequencing analysis confirmed the m.3243A > G transition, and excluded the three most common LHON mutations, as well as the m.3376G > A LHON/MELAS overlap syndrome mutation. Based on the constellation of clinical symptoms and signs presented in our patient, including the muscular involvement, and the results of the investigations, the diagnosis of optic neuropathy as a stroke-like event affecting the optic disc was performed. L-arginine and ubidecarenone therapies were started with the aim to improve stroke-like episode symptoms and prevention. The visual defect remained stable with no further progression or outbreak of new symptoms. CONCLUSIONS: Atypical clinical presentations must be always considered in mitochondrial disorders, even in well-described phenotypes and when mutational load in peripheral tissue is low. Mitotic segregation of mitochondrial DNA (mtDNA) does not allow to know the exact degree of heteroplasmy existent within different tissue, such as retina and optic nerve. Important therapeutic implications arise from a correct diagnosis of atypical presentation of mitochondrial disorders.

Delaying anti-VEGF therapy during the COVID-19 pandemic: long-term impact on visual outcomes in patients with neovascular age-related macular degeneration.

OBJECTIVES: To evaluate the outcomes of delayed intravitreal injections (IVIs) caused by the outbreak of coronavirus disease 2019 (COVID-19), in patients with neovascular age-related macular degeneration (nAMD). METHODS: nAMD patients with scheduled IVIs between March 1st and April 30th, 2020 were stratified through a risk-based selection into a non-adherent group (NA-group) if they skipped at least one IVI and an adherent group (A-group) if they followed their treatment schedule. During the pandemic visit (v0), if a significant worsening of the disease was detected, a rescue therapy of three-monthly IVIs was performed. Multimodal imaging and best-corrected visual acuity (BCVA) findings were evaluated after 6 months (v6), compared between groups and with the visit prior the lockdown (v-1). RESULTS: Two hundred fifteen patients (132 females, mean age: 81.89 ± 5.98 years) delayed their scheduled IVI while 83 (53 females, mean age: 77.92 ± 6.06 years) adhered to their protocol. For both groups, BCVA at v0 was significantly worse than v-1 (mean 4.15 ± 7.24 ETDRS letters reduction for the NA-group and 3 ± 7.96 for the A-group) but remained stable at v6. The two groups did not significantly differ in BCVA trends after 6 months and neither for development of atrophy nor fibrosis. CONCLUSIONS: A risk-based selection strategy and a rescue therapy may limit the long-term outcomes of an interruption of the treatment protocol in patients with nAMD.

RESPONSE TO TREATMENT OF CHOROIDAL NEOVASCULARIZATION IN HIGHLY MYOPIC EYES WITH DOME-SHAPED MACULA: Two Years of Follow-Up.

PURPOSE: To compare the 2-year outcome to antivascular endothelial growth factor therapy for myopic choroidal neovascularization (CNV) in the eyes with or without dome-shaped macula (DSM). METHODS: Data from treatment-naive myopic CNV with a 2-year follow-up were retrospectively collected and divided into two groups according to the presence of DSM. The best-corrected visual acuity was acquired at baseline, 3, 12, and 24 months. The association between visual outcomes and CNV type and area, presence of scleral-derived feeder vessel, macular atrophy, and lacquer cracks at baseline was also evaluated. RESULTS: Fifty-four eyes of 54 patients were included; 18 eyes (33.4%) had DSM. Choroidal neovascularization was foveal in 10 DSM eyes (55.6%) and in 30 non-DSM eyes (83.9%), P = 0.033. At baseline, the mean best-corrected visual acuity was significantly higher in the DSM group (68.33 ± 12.04 Early Treatment Diabetic Retinopathy Study letters, 20/40 Snellen) compared with the non-DSM group (57.75 ± 13.46 Early Treatment Diabetic Retinopathy Study letters, 20/72 Snellen; P = 0.007). This difference disappeared after 3 months and did not reoccur afterward. All other parameters were not significantly associated with visual outcomes. CONCLUSION: Overall, DSM does not represent a negative prognostic factor in response to antivascular endothelial growth factor therapy in myopic CNVs after 2 years. However, in DSM eyes, CNVs tend to be extrafoveal, thus ensuring a good visual prognosis from the earliest stage of the disease.

ACUTE IDIOPATHIC MACULOPATHY: A Proposed Disease Staging Based on Multimodal Imaging.

PURPOSE: To describe the clinical course and the multimodal imaging of acute idiopathic maculopathy. METHODS: Medical records and multimodal imaging including color fundus photography, optical coherence tomography, and fundus autofluorescence were retrospectively reviewed. Recognition of the fundus autofluorescence patterns and their relationship with the disease duration, best-corrected visual acuity, and optical coherence tomography features represented the main outcome measures. RESULTS: Seventeen eyes of 16 patients (7 women; mean age 29.9 years) with a mean follow-up of 23.9 months were included. The mean best-corrected visual acuity at presentation was 0.63 ± 0.54 logarithm of the minimum angle of resolution (Snellen equivalent, 20/85). All but one patient had the best-corrected visual acuity recovery to 20/20. Four sequential patterns of fundus autofluorescence corresponding to 4 proposed stages of disease were observed. Patterns 1 (central hypoautofluorescence with surrounding hyperautofluorescence) and 2 (stippled hyperautofluorescence and hypoautofluorescence) were found at presentation. Patterns 3 (central hyperautofluorescence surrounded by hypoautofluorescence) and 4 (hypoautofluorescence) were observed during the disease course and/or at the last follow-up visit. Duration of the disease was significantly different between patterns at baseline and last visit. Pattern 1 significantly related to the presence of subretinal detachment (Fisher's exact test; P =0.003) on optical coherence tomography in comparison with Pattern 2. Pattern 4 showed unique homogeneously decreased autofluorescence with corresponding attenuation of retinal pigment epithelium and restored outer retinal layers on optical coherence tomography. CONCLUSION: A sequential disease staging based on multimodal imaging for acute idiopathic maculopathy is proposed. The recognition of the observed imaging patterns may help clinicians in the correct diagnosis and patient counseling.

Evidence of retinal anterograde neurodegeneration in the very early stages of multiple sclerosis: a longitudinal OCT study.

BACKGROUND: Neurodegenerative processes are present since the early stages of multiple sclerosis (MS), constituting the primary substrate of disability. As part of the CNS, retinal damage could be considered a reliable prognostic biomarker of neurodegeneration in MS. OBJECTIVES: To characterize longitudinal changes in the retinal layers' thickness and to investigate correlations between retinal atrophy and other prognostic biomarkers, i.e., cerebrospinal fluid (CSF) ß-amyloid1-42 (Aß) levels. METHODS: Forty-two eyes without a history of optic neuritis of 23 MS patients were recruited. All patients underwent spectral-domain-OCT scans (SD-OCT), brain magnetic resonance imaging (MRI), and lumbar puncture at baseline. SD-OCT and brain MRI were repeated after 12 months. Ten controls underwent the same OCT procedure. RESULTS: At baseline, macular ganglion cell/inner plexiform layer (mGCIPL) thickness was reduced in patients compared to controls (p = 0.008), without retinal nerve fiber layer (RNFL) thinning, that was revealed only at follow-up (p = 0.005). Patients with lower CSF Aß levels displayed reduced RNFL thickness values, both at baseline and follow-up. CONCLUSIONS: At very early clinical stages, mGCIPL thickness values were reduced without a concomitant peripapillary RNFL thinning. The longitudinal assessment demonstrated a RNFL loss in patients compared to HC, together with a plateau of mGCIPL thinning. Aßlow subgroup of patients showed a reduction of retinal nerve fiber layer thickness.

The loss of macular ganglion cells begins from the early stages of disease and correlates with brain atrophy in multiple sclerosis patients.

BACKGROUND: The importance of neurodegeneration in multiple sclerosis (MS) is increasingly well recognized. OBJECTIVES: To evaluate retinal pathology using optical coherence tomography (OCT) and to investigate possible associations between retinal layers' thickness and specific patterns of gray matter volume in patients with a new diagnosis of MS. METHODS: A total of 31 patients underwent OCT scans and brain magnetic resonance imaging. In total, 30 controls underwent the same OCT procedure. The association between focal cortical volume and OCT measurements was investigated with voxel-based morphometry (VBM). RESULTS: Compared to controls, patients' macular retinal nerve fiber layer (mRNFL), macular ganglion cell layer (mGCL), macular inner plexiform layer (mIPL), and macular ganglion cell-inner plexiform layer (mGCIPL) thickness were significantly reduced ( p = 0.0009, p = 0.0003, p = 0.0049, and p = 0.0007, respectively). Peripapillary RNFL (pRNFL) and temporal sector pRNFL (T-pRNFL) did not show any significant changes, although there was a trend toward T-pRNFL thinning ( p = 0.0254). VBM analysis showed that mGCIPL and pRNFL were significantly correlated with the volume reduction of occipital-parietal cortex ( p < 0.005). CONCLUSION: mRNFL, mGCL, and mIPL are significantly reduced in MS patients without concomitant pRNFL thinning. These retinal changes show a significant association with cortical regions that are known to be important for visuospatial performance.

Sickle cell maculopathy: Identification of systemic risk factors, and microstructural analysis of individual retinal layers of the macula.

PURPOSE: To identify systemic risk factors for sickle cell maculopathy, and to analyze the microstructure of the macula of Sickle Cell Disease (SCD) patients by using automated segmentation of individual retinal layers. METHODS: Thirty consecutive patients with SCD and 30 matched controls underwent spectral-domain optical coherence tomography (SD-OCT) and automated thickness measurement for each retinal layer; thicknesses for SCD patients were then compared to normal controls. Demographic data, systemic data, and lab results were collected for each SCD patient; multivariate logistic regression analysis was used to identify potential risk factors for sickle cell maculopathy. RESULTS: Ongoing chelation treatment (p = 0.0187) was the most predictive factor for the presence of sickle cell maculopathy; the odds were 94.2% lower when chelation was present. HbF level tended to influence sickle cell maculopathy (p = 0.0775); the odds decreased by 12.9% when HbF increased by 1%. Sickle cell maculopathy was detected in 43% of SCD patients as patchy areas of retinal thinning on SD-OCT thickness map, mostly located temporally to the macula, especially in eyes with more advanced forms of sickle cell retinopathy (p = 0.003). In comparison to controls, SCD patients had a subtle thinning of the overall macula and temporal retina compared to controls (most p<0.0001), involving inner and outer retinal layers. Thickening of the retinal pigment epithelium was also detected in SCD eyes (p<0.0001). CONCLUSIONS: Chronic chelation therapy and, potentially, high levels of HbF are possible protective factors for the presence of sickle cell maculopathy, especially for patients with more advanced forms of sickle cell retinopathy. A subtle thinning of the overall macula occurs in SCD patients and involves multiple retinal layers, suggesting that ischemic vasculopathy may happen in both superficial and deep capillary plexi. Thinning of the outer retinal layers suggests that an ischemic insult of the choriocapillaris may also occur in SCD patients.

Drusen-like Deposits in Young Adults Diagnosed With Systemic Lupus Erythematosus.

PURPOSE: To determine the prevalence of drusen-like deposits (DLDs) and choroidal changes in patients with systemic lupus erythematosus (SLE), with or without glomerulonephritis; and to correlate ocular findings with systemic features. DESIGN: Case-control study. METHODS: Sixty patients with SLE (age, 18-55 years; 30 with and 30 without SLE-related glomerulonephritis) and 60 age- and sex-matched healthy controls were enrolled. All patients underwent noninvasive multimodal imaging that included fundus photography, near-infrared reflectance, blue autofluorescence, blue reflectance, and spectral-domain optical coherence tomography (SDOCT). Images were analyzed for the prevalence of DLDs. Distribution, size, and number of DLDs were measured. Correlations between ocular findings and systemic features were analyzed. Subfoveal choroidal thickness (SCT) was measured using the SDOCT. RESULTS: Drusen-like deposits were detected in 40% of SLE subjects and 3.33% of controls (P < .0001). Compared with other techniques, SDOCT detected the largest number of affected subjects. In eyes with DLDs, small, medium, and large lesions were found in 75%, 50%, and 42% of cases, respectively. Drusen-like deposits were located in the nasal, temporal, inferior, superior, and central regions of the posterior pole in 83%, 75%, 67%, 54%, and 25% of eyes, respectively. The prevalence of DLDs in patients with SLE was similar regardless of renal involvement, but patients with glomerulonephritis had more DLDs per eye, larger deposits, and DLDs in >3 quadrants (P < .001, P = .03, P = .009, respectively). Subfoveal choroidal thickness was greater in patients with SLE (P = .002). CONCLUSIONS: Drusen-like deposits in patients with SLE were independent of renal disease and were best detected with SDOCT. Lupus-related glomerulonephritis was associated with more fundus abnormalities and a screening SDOCT should be considered in all patients with SLE. Drusen-like deposits in the absence of glomerulonephritis may support the recent proposal that complement alteration is the primary cause of these lesions.

Sudden occurrence of Roth spots and retinal hemorrhages following endoscopic adhesiolysis: an SD-OCT evaluation.

PURPOSE: To document the occurrence of Roth spots and retinal hemorrhages by spectral-domain optical coherence tomography (SD-OCT) following endoscopic adhesiolysis for failed back surgery syndrome. METHODS: Case report. RESULTS: A 47-year-old patient noted progressive and bilateral visual loss immediately after epidural endoscopy and endoscopic adhesiolysis. Funduscopic examination showed multiple Roth spots and retinal hemorrhages at the posterior pole and the retinal midperiphery in both eyes. Spectral-domain optical coherence tomography demonstrated that Roth spots involved the inner retina, while dot hemorrhages involved the outer retina. Most retinal hemorrhages and Roth spots resolved over 6 weeks, with complete functional recovery in both eyes. However, SD-OCT revealed multiple areas of disruption of the outer retinal layers in the left eye. CONCLUSIONS: Roth spots and retinal hemorrhages can occur after endoscopic spinal surgery. Although hemorrhages resolve quickly over few weeks, SD-OCT can demonstrate that retinal damage might persist, especially in the outer retina. This finding may explain cases of incomplete recovery of visual function after complicated endoscopic adhesiolysis.

Functional and Structural Abnormalities in Deferoxamine Retinopathy: A Review of the Literature.

Deferoxamine mesylate (DFO) is the most commonly used iron-chelating agent to treat transfusion-related hemosiderosis. Despite the clear advantages for the use of DFO, numerous DFO-related systemic toxicities have been reported in the literature, as well as sight-threatening ocular toxicity involving the retinal pigment epithelium (RPE). The damage to the RPE can lead to visual field defects, color-vision defects, abnormal electrophysiological tests, and permanent visual deterioration. The purpose of this review is to provide an updated summary of the ocular findings, including both functional and structural abnormalities, in DFO-treated patients. In particular, we pay particular attention to analyzing results of multimodal technologies for retinal imaging, which help ophthalmologists in the early diagnosis and correct management of DFO retinopathy. Fundus autofluorescence, for example, is not only useful for screening patients at high-risk of DFO retinopathy, but is also a prerequisite for identify specific high-risk patterns of RPE changes that are relevant for the prognosis of the disease. In addition, optical coherence tomography may have a clinical usefulness in detecting extent and location of different retinal changes in DFO retinopathy. Finally, this review wants to underline the need for universally approved guidelines for screening and followup of this particular disease.

Longitudinal modifications of the Ozurdex intravitreal implant as imaged by SD-OCT.

PURPOSE: To describe in vivo longitudinal modifications of the Ozurdex intravitreal implant using spectral-domain optical coherence tomography (SD-OCT) over a 6-month period in an eye treated for retinal vein occlusion (RVO). METHODS: Case report. RESULTS: An 82-year-old woman with severe macular edema secondary to branch RVO received an Ozurdex intravitreal implant in the left eye. At day 1, SD-OCT showed that the implant was completely filled with highly reflective dexamethasone. At day 30, complete resolution of macular edema on SD-OCT was noted. At day 60, macular edema started to relapse; SD-OCT scans over the implant showed highly reflective borders that appeared irregular and focally retracted, while the majority of the internal drug had been washed out. At day 180, macular edema returned to baseline levels; SD-OCT scans over the implant showed that the device was contracted with almost complete absence of the internal lumen and drug. CONCLUSIONS: Using SD-OCT, we demonstrated that 60 days postinjection most dexamethasone had been released from the Ozurdex implant, which showed multiple irregularities. This was associated with recurrence of macular edema that became worse after 180 days, when there was no residual dexamethasone remaining in the shrunken implant. Low steady levels of the drug in the vitreous and lower biological activity in the retina after the 2-month high-dose release phase may explain why a large number of patients lose clinical improvement 60 days postinjection, as shown by pivotal clinical trials.

Choroidal findings in dome-shaped macula in highly myopic eyes: a longitudinal study.

PURPOSE: To describe choroidal findings in dome-shaped macula associated with high myopia using fluorescein angiography (FA), indocyanine green angiography (ICGA), and spectral-domain optical coherence tomography (SD OCT), and to elucidate the mechanism and natural course of serous retinal detachment (RD) associated with dome-shaped macula. DESIGN: Retrospective, observational case series. METHODS: We reviewed longitudinal imaging results of 52 highly myopic eyes with dome-shaped macula. Changes on FA and ICGA were assessed. Retinal, choroidal, and scleral thicknesses and bulge height were measured on SD OCT. RESULTS: Serous RD was the most common abnormality associated with dome-shaped macula, detected by SD OCT in 44% of the cases with no associated choroidal neovascularization. Significant differences in the proportion of eyes with pinpoint leakage on FA (P < .001), punctate hypercyanescence on ICGA (P < .001), and pigment epithelium detachment on SD OCT (P < .001) were noted inside the inward bulge of the staphyloma between eyes with and without serous RD. Serous RD was not associated with hyperpermeability areas on ICGA. Eyes with serous RD had thicker choroid (P = .004) and tended to have thicker sclera (P = .067) and greater bulge height (P = .079). Choroidal thickness, scleral thickness, and bulge height were positively correlated (P < .01). All eyes presented a fluctuating course of serous RD during follow-up. Worsening of serous RD was associated with appearance of new punctate hypercyanescent spots on ICGA and leaking points on FA (P < .001 and P = .016, respectively). CONCLUSION: Serous RD in dome-shaped macula was likely caused by choroidal vascular changes, similar to central serous chorioretinopathy, but specifically confined in the inward bulge of the staphyloma and secondary to excessive scleral thickening. Serous retinal detachment showed fluctuating changes over time, with alternating active and inactive stages. Angiographic findings in dome-shaped macula suggest the choroid as a target for possible treatment strategies.

The spectrum of ocular alterations in patients with ß-thalassemia syndromes suggests a pathology similar to pseudoxanthoma elasticum.

PURPOSE: To determine the prevalence and spectrum of ocular fundus abnormalities in patients with ß-thalassemia and to investigate risk factors for their development. DESIGN: Cross-sectional, observational study. PARTICIPANTS: A total of 255 patients with ß-thalassemia major (TM) and ß-thalassemia intermedia (TI) were consecutively recruited and investigated. METHODS: Patients underwent best correct visual acuity, indirect ophthalmoscopy, and fundus photography, including fundus autofluorescence (FAF) and near-infrared reflectance imaging using a confocal scanning laser ophthalmoscope (cSLO). Hematologic parameters were determined, including mean ferritin levels, aspartate amino transferase, alanine amino transferase, calcium, pre-transfusion hemoglobin, history of splenectomy, and liver iron concentration. Factors associated with the ocular phenotype were assessed using logistic regression. MAIN OUTCOME MEASURES: Ocular phenotype as determined by clinical examination and used multimodal imaging. RESULTS: A total of 153 patients (60.0%) affected by TM and 102 patients (40.0%) affected by TI participated, of whom 216 (84.7%) were receiving iron-chelating therapy. Ocular fundus abnormalities characteristic of pseudoxanthoma elasticum (PXE) were detected by cSLO in 70 of 255 patients (27.8%) and included peau d'orange (19.6%), angioid streaks (12.9%), pattern dystrophy-like changes (7.5%), and optic disc drusen (2.0%). Pseudoxanthoma elasticum-like changes were more frequent in patients with TI (P<0.001). Patients with PXE-like fundus changes were older than patients without these fundus changes (P<0.001). In both patients with TI and TM, age (P = 0.001) and splenectomy (P = 0.001) had the strongest association with presence of PXE-like fundus changes in multivariate analyses. A total of 43 of 255 patients (16.9%) showed increased retinal vascular tortuosity independently of the PXE-like fundus changes, which was associated with aspartate amino transferase (P = 0.036), hemoglobin (P = 0.008), and ferritin levels (P = 0.005). CONCLUSIONS: Pseudoxanthoma elasticum-like fundus changes are a frequent finding in patients with ß-thalassemia. In TI, these changes increase with duration or severity of the disease. This particular ocular phenotype suggests an ocular pathology similar to PXE. Retinal vascular tortuosity may be an additional disease manifestation independent of the PXE-like syndrome. Patients with long-standing disease requiring iron-chelating treatment and a history of splenectomy need regular ophthalmic checkups because they are at risk of developing PXE-like fundus changes and potentially of subsequent choroidal neovascularization.

Choroidal volume variations during childhood.

PURPOSE: We analyzed choroidal volume (CV) variations during childhood using enhanced depth imaging optical coherence tomography, and evaluated its association with age, axial length (AXL), sex, weight, and height. METHODS: Imaging studies of the right eyes of 52 healthy children were reviewed and included in this study. Subjects underwent a complete ocular examination and AXL measurement, as well as a raster macular scan using the Heidelberg Spectralis device. The choroid was segmented manually. RESULTS: Subjects included 21 males and 31 females, with mean age of 9 years (range, 2-17 years) and mean AXL of 22.8 ± 0.98 mm. Mean CV was 0.263 ± 0.068 mm(3) for the foveal circle and 8.545 ± 1.822 mm(3) for the total Early Treatment of Diabetic Retinopathy Study (ETDRS) grid. The CV of the nasal quadrant was significantly lower than all others (P < 0.001). Total and foveal CV showed significant negative correlation with AXL after adjustment for age (P < 0.001), and significant positive correlation with age after adjustment for AXL (P < 0.001). Total CV was correlated significantly with sex after adjusting for AXL (P = 0.01), while no correlations were found between total CV and height or weight. The CV increased by 0.214 mm(3) (2.5%) for every year, and decreased by 1.0 mm(3) (11.7%) for every millimeter of axial length. Regression analysis confirmed a trend of higher CV in females than in males (P = 0.056). CONCLUSIONS: The CV increases with age during childhood, but decreases with AXL. This finding supports the hypothesis that the choroid grows progressively during childhood. Intersexual differences of CV also may be present.

Abnormal fundus autofluorescence results of patients in long-term treatment with deferoxamine.

PURPOSE: To describe and classify patterns of abnormal fundus autofluorescence (FAF) of patients with ß-thalassemia receiving long-term treatment with deferoxamine (DFO). DESIGN: Prospective, cross-sectional, case-control study. PARTICIPANTS: A total of 197 consecutive patients with ß-thalassemia major or intermedia with at least 10 years of treatment with DFO were recruited in a tertiary referral center in Milan, Italy, and were investigated. Seventy-nine thalassemic patients without a history of chelation therapy were included as a control group. METHODS: All of the patients were investigated using best-corrected visual acuity (BCVA), fundus photography, and FAF imaging by confocal scanning laser ophthalmoscopy (cSLO) and were compared with the control group. MAIN OUTCOME MEASURES: Identification of abnormal FAF patterns in thalassemic patients treated with long-term DFO and their progression and relationship with visual function. RESULTS: Abnormal FAF not related to other diseases was observed in 18 of the 197 patients (9%) and was classified into 4 phenotypic patterns: minimal change, focal, patchy, and speckled. The abnormal increased or decreased FAF was bilateral in all the cases, and only in some cases did it correspond to funduscopically visible alterations. There were no FAF abnormalities in the control group. During the follow-up, progressive FAF changes related to retinal pigment epithelium (RPE) damage occurred in the patchy pattern, associated with decreasing BCVA. Patients with speckled and focal patterns showed limited or no changes in FAF during the follow-up. No changes in FAF were found in patients with a minimal change pattern. No treated patient with a normal baseline examination demonstrated FAF changes. Patients with patterns other than the minimal change showed significant BCVA deterioration (P<0.001). CONCLUSIONS: Various phenotypic patterns of abnormal FAF can be identified with cSLO imaging. Fundus autofluorescence is a helpful, fast, and noninvasive tool for monitoring the status of the macula in patients at risk of DFO toxicity. It may be useful in the decision to discontinue or switch the therapy in cases of particular high risk for disease progression. The progressive alteration of the RPE suggests an important role of pathologic RPE changes in the evolution of visual loss during long-term treatment with DFO.