Final versus referral diagnosis of childhood visual impairment in an Italian tertiary low vision rehabilitation centre.

PURPOSE: To compare the final diagnosis of the causes of low vision in children attending a tertiary rehabilitation centre for visually impaired children versus referral diagnosis. METHODS: Retrospective review of clinical charts of all children referred to the Robert Hollman Foundation, a tertiary centre for visually impaired children, between January 2010 and June 2011. The following clinical data were analysed: entry diagnosis made by the referral ophthalmologist and final diagnosis made at Robert Hollman Foundation based on a complete ophthalmic evaluation. RESULTS: Ninety-two consecutive children (mean age = 2.37 ± 1.98 years, range = 0-9) were included. A referral diagnosis was retrieved in 76 cases (82.6%), including cerebral visual impairment (14.1%), retinopathy of prematurity (14.1%), hereditary retinal diseases (10.9%), nystagmus (8.7%) and other rarer diseases (34.8%). In the remaining 16 children (17.4%), a precise referral diagnosis was unavailable. Final clinical diagnosis made at Robert Hollman Foundation was normal visual function in 8.7%, cerebral visual impairment in 30.4%, retinopathy of prematurity in 10.9%, hereditary retinal disease in 9.8% and other in 40.2%. In 17 cases (18.5%), the diagnosis made at the Robert Hollman Foundation did not confirm the entry diagnosis. Among patients where measurement of visual acuity was possible (84), 66.7% were blind or seriously visual impaired, and the main causes were cerebral visual impairment (32.1%) and retinopathy of prematurity (16.1%). CONCLUSION: The most frequent diseases were cerebral visual impairment, retinopathy of prematurity and hereditary retinal diseases. Approximately one-third of referred children had not a correct diagnosis at baseline. The activity of an ophthalmic tertiary centre is essential to offer a precise diagnosis to visually impaired (sometimes with other deficits) children.

MORPHOFUNCTIONAL EVALUATION OF MACULAR-FOVEAL CAPILLARIES: A Comparative Optical Coherence Tomography Angiography and Microperimetry Study.

PURPOSE: To analyze the macular function of eyes with macular-foveal capillaries (MFC), a condition characterized by the absence of the foveal avascular zone (FAZ), identified by optical coherence tomography angiography. METHODS: Eight eyes with MFC at optical coherence tomography angiography and normal visual acuity were consecutively recruited. Eight eyes of healthy subjects were enrolled as healthy controls. All eyes underwent optical coherence tomography, optical coherence tomography angiography, best-correct visual acuity, low-luminance visual acuity, contrast sensitivity measurement, colour vision tests, and both mesopic and scotopic microperimetry. RESULTS: Best-corrected visual acuity, low-luminance visual acuity, contrast sensitivity, and colour vision tests did not differ between the two groups. At mesopic microperimetry, both foveal retinal sensitivity and mean mesopic retinal sensitivity of the central 1° were statistically inferior in MFC versus control eyes (P < 0.0001 and P < 0.0001, respectively). At scotopic microperimetry, a dense foveal scotoma, normally present in control eyes, was completely lacking in MFC eyes. Scotopic foveal retinal sensitivity was statistically superior in MFC versus control eyes (P = 0.009). CONCLUSION: The absence of the foveal dense scotoma in scotopic conditions underlines that the foveal rod-free zone is not present when capillaries are present in this area. An anomalous foveal distribution of photoreceptors, with both rods and cones present in this area, may be postulated in MFC eyes.

Early OCT angiography changes of type 1 CNV in exudative AMD treated with anti-VEGF.

AIMS: To investigate, with optical coherence tomography angiography (OCTA), short-term changes of type 1 choroidal neovascularisation (CNV), secondary to exudative age-related macular degeneration, after anti-vascular endothelial growth factor (VEGF) treatment. METHODS: Patients affected by type 1 CNV treated with intravitreal anti-VEGF were consecutively enrolled. All patients underwent OCTA examination before and 48 hours after anti-VEGF treatment. Quantitative and qualitative vascular and morphological macular changes were evaluated. RESULTS: Sixteen eyes were included (11 treated with aflibercept and 5 with ranibizumab). Both CNV mean area and pigment epithelium detachment significantly reduced (p=0.0004 and p=0.0007, respectively) after treatment. Cystoid macular oedema (four eyes) decreased in all cases. Neuroretinal detachment (13 eyes) decreased in 85% of cases (11 eyes). Fine CNV vessels density decreased in 75% (12 eyes), whereas larger CNV vessels density remained stable in 66.7% (10 eyes), choroidal flow void signal (7 eyes at baseline) increased in 42.9% (3 eyes) of them and remained stable in 57.1% (4 eyes). Interoperator reproducibility for OCT examination was good for all measurements (intraclass correlation coefficient>0.65). CONCLUSION: Early remodelling of type 1 CNV network after treatment may be non-invasively and reproducibly analysed by means of OCTA. Choroidal perfusion impairment, choroidal flow void signal, surrounding CNV may change during treatment.

Single Retinal Layer Changes After Subthreshold Micropulse Yellow Laser in Diabetic Macular Edema.

A pilot prospective, interventional study has been conducted on 10 patients with diabetic macular edema (DME) treated with subthreshold micropulse laser (SMPL) to evaluate changes of individual retinal layers and to correlate with functional changes. All patients underwent complete ophthalmologic evaluation including spectral-domain optical coherence tomography (OCT) and microperimetry at baseline, 3 months, 6 months, 9 months, and 12 months. Compared with baseline, a significant decrease was found in inner nuclear layer (INL) and outer retinal layer (ORL) thickness in the central 1 mm (P < .05). Increase in best-corrected visual acuity was significantly and inversely correlated to central retinal thickness (CRT) (P = .0027), INL (P = .0167), and outer nuclear layer (ONL) thickness (P = .0107). Increase in retinal sensitivity was significantly and inversely correlated to CRT and ONL thickness (P < .01). Therefore, SMPL showed to improve firstly functional parameters and then morphologic parameters. Functional parameters were inversely correlated to CRT, INL, and ONL thickness. The exact mechanism of reduction of INL thickness induced by SMPL remains to be further evaluated. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e218-e225.].

Repeatability and Reproducibility of Foveal Avascular Zone Area Measurement on Normal Eyes by Different Optical Coherence Tomography Angiography Instruments.

PURPOSE: To compare the foveal avascular zone (FAZ) area measurements produced by different optical coherence tomography angiography (OCTA). METHODS: Healthy enrolled volunteers underwent OCTA using 2 different devices: Spectralis HRA+OCTA (Heidelberg Engineering, Heidelberg, Germany) and RS-3000 Advance (Nidek, Gamagori, Japan). Two graders measured FAZ in both superficial (SCP) and deep (DCP) retinal capillary plexuses. The SCP and DCP en face images were visualized automatically segmenting 2 separate slabs defined by the arbitrary segmentation lines created by the software of each OCT device. One grader repeated each measure twice. RESULTS: Fifty-nine eyes were included. The mean FAZ was 0.33 ± 0.09 mm2 at the SCP and 0.57 ± 0.17 mm2 at the DCP measured with RS-3000 versus 0.30 ± 0.08 and 0.35 ± 0.08 mm2, respectively, measured with Spectralis. The measurements of the 2 devices were significantly different (p < 0.0001). The intraoperator agreement was excellent at the SCP (intraclass correlation coefficient, ICC: 0.97 with Spectralis and 0.96 with RS-3000). At the DCP, it was good with Spectralis and fair with RS-3000 (ICC: 0.85 and 0.64, respectively). The interoperator agreement was excellent for Spectralis and good for RS-3000 at the SCP (ICC: 0.97 and 0.93, respectively). It was good at the DCP with both devices (ICC: 0.74 with RS-3000 and 0.81 with Spectralis). CONCLUSIONS: FAZ measurements obtained with different OCTA devices differ. These findings should be considered in follow-up studies of patients with retinal vascular diseases.

MORPHOFUNCTIONAL EVALUATION IN DOME-SHAPED MACULA: A MICROPERIMETRY AND OPTICAL COHERENCE TOMOGRAPHY STUDY.

PURPOSE: To investigate retinal sensitivity (Se) in dome-shaped macula (DSM) using microperimetry and to correlate functional findings to specific spectral domain optical coherence tomography features. METHODS: Patients affected by DSM in at least 1 eye were consecutively enrolled in a prospective, cross-sectional study. All studied eyes performed best-corrected visual acuity measurement, microperimetry to assess Se and optical coherence tomography to investigate DSM pattern and to measure bulge height and retinal and choroidal thicknesses. RESULTS: Fifty-three eyes of 29 patients were studied. Dome-shaped macula was vertically oriented (V-DSM) in 23 (43.4%), symmetric (S-DSM) in 17 (32.1%), and horizontally oriented (H-DSM) in 13 eyes (24.5%). Foveal subretinal fluid was present in 29/53 (54.7%) cases; it correlated to the bulge height (P < 0.0001) and determined a reduction of Se (P < 0.0001) not of best-corrected visual acuity (P = 0.7105). Mean Se was 13.9 ± 3.2 dB. Microperimetry parameters did not differ among the different DSM patterns. However, Se was significantly impaired if foveal subretinal fluid was present in V-DSM and in S-DSM, but not in H-DSM (V-DSM: P < 0.0001; S-DSM: P = 0.0252; H-DSM: P = 0.5723). In H-DSM, inferior choroidal thickness was thicker in cases with foveal subretinal fluid compared with those without it (P = 0.0363). CONCLUSION: In DSM, Se evaluation better reflects the central functional impairment than best-corrected visual acuity, particularly when some optical coherence tomography features, such as foveal subretinal fluid and higher bulge height, are present.

RETINAL VASCULAR ABNORMALITIES IN A LARGE COHORT OF PATIENTS AFFECTED BY NEUROFIBROMATOSIS TYPE 1: A Study Using Optical Coherence Tomography Angiography.

PURPOSE: To evaluate the prevalence, the vascular features, and the clinical diagnostic implication of retinal vascular abnormalities (RVAs) associated with neurofibromatosis Type 1 (NF1) in a large cohort of patients. METHODS: Two hundred and ninety-four patients affected by NF1 were consecutively enrolled. The presence of RVAs was detected by means of infrared confocal scanning laser ophthalmoscopy images. Three hundred age- and race-matched healthy subjects were enrolled as a healthy control group. Fluorescein angiography, indocyanine green angiography, and optical coherence tomography angiography were also performed in patients with RVAs. RESULTS: Retinal vascular abnormalities were detected in 18 patients with NF1 (6.1%) and in none of the healthy subjects. Retinal vascular abnormalities appeared in all cases as well-defined, small, tortuous retinal vessels with a spiral aspect, originating from small tributaries of retinal veins. The presence of RVAs did not correlate with the presence of other specific ocular or systemic NF1 features (P > 0.05). On optical coherence tomography angiography, RVAs appeared as an isolated tortuous vessel of the superficial vascular plexus in all cases, associated with localized anomalous crowded and congested capillary network of the deep vascular plexus in 75% of cases. CONCLUSION: Retinal vascular abnormalities are present in a limited proportion of patients affected by NF1 and can be considered an additional distinctive sign of the disease.

Diabetic Macular Edema With and Without Subfoveal Neuroretinal Detachment: Two Different Morphologic and Functional Entities.

PURPOSE: To assess specific morphologic and functional characteristics in eyes with diabetic macular edema (DME) with subfoveal neuroretinal detachment (SND+) vs DME without SND (SND-). DESIGN: Cross-sectional, prospective, comparative case series. METHODS: Seventy-two patients (72 eyes: 22 eyes SND+ and 50 eyes SND-) with treatment-naïve, center-involving DME were evaluated. Data gathering included fundus color photographs, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), best-corrected visual acuity (BCVA), and microperimetry. The following parameters were evaluated with SD-OCT: central macular thickness (CMT [including SND]); central retinal thickness (CRT [excluding SND]); choroidal thickness (CT); nasal and temporal retinal thickness (RT) at 500 µm and 1500 µm from the fovea; the number of hyperreflective retinal spots (HRS) in the central 3000 µm; and the presence of SND and integrity of the external limiting membrane (ELM). Retinal sensitivity (RS) was evaluated within 4 degrees and 12 degrees of the fovea. Correlation among CT, RS, and HRS in patients with and without SND was determined. RESULTS: CMT (P = .032), temporal RT at 1500 µm (P = .03), mean CT (P = .009), and mean number of HRS (P = .0001) were all higher in SND+ vs SND- eyes. CRT, BCVA, HbA1c, and prevalence of systemic arterial hypertension were not different between the 2 groups. RS within 4 degrees (P = .002) and 12 degrees (P = .015) was lower in SND+ vs SND- eyes. SND correlated significantly with disruption of the ELM (54.55% vs 24%, P = .01) and lower RS. A direct correlation was found between the number of HRS, presence of SND, CT, and RS within 12 degrees in SND- eyes, and an inverse correlation was found between CT and RS within 12degrees in SND+ eyes. CONCLUSIONS: These data may improve characterization of DME in eyes with SND. DME with SND correlates with greater CT, more HRS, disruption of the ELM, and significant macular functional impairment (RS decrease) vs SND-.

Long-term longitudinal modifications in mesopic microperimetry in early and intermediate age-related macular degeneration.

PURPOSE: To evaluate functional changes (retinal sensitivity and fixation characteristics) determined by microperimetry in patients with early and intermediate AMD over 6 years. METHODS: Prospective, longitudinal follow-up (FU) study of 16 patients (29 eyes) with early and intermediate AMD (AREDS 2 and AREDS 3 classification). All eyes underwent: complete ophthalmic examination with best corrected visual acuity (BCVA) determination, color fundus photo (CFP), optical coherence tomography and microperimetry. All CFP were evaluated by two retinal specialists masked to functional data for changes in severity of clinical features over the course of FU. RESULTS: Of 17 eyes graded as AREDS 2 at baseline, 14 (82.35 %) remained stable, and 3 (18.75 %) progressed to AREDS 3. Of 12 eyes graded as AREDS 3 at baseline, 10 remained stable (83.33 %), and 2 (16.67 %) progressed to AREDS 4. Mean BCVA significantly deteriorated in both AREDS 2 (p = 0.006) and AREDS 3 (p = 0.016), with greater decrease in AREDS 3 (p = 0.01)6. Mean retinal sensitivity (RS) significantly decreased over time in both AREDS 2 (p < 0.0001) and AREDS 3 group (p = 0.002), with greater decrease in AREDS 3 (p = 0.006). The mean number of dense scotomas did not change in AREDS 2 (p = 0.3), but significantly increased in the AREDS 3 group (p = 0.035). Points with decreased RS were located in all but the central point (p < 0.0001 for all), without significant differences in number among rings. In the AREDS 2 group, fixation stability remained unchanged. In the AREDS 3 group, four eyes deteriorated from stable to unstable fixation at FU (p = 0.045). CONCLUSION: A significant deterioration in RS is reported in early and intermediate AMD eyes, whereas fixation stability changed only in intermediate AMD (AREDS 3) over long-term follow-up. Microperimetry examination can become a new functional biomarker in early and intermediate AMD patients.

Imaging retinal inflammatory biomarkers after intravitreal steroid and anti-VEGF treatment in diabetic macular oedema.

PURPOSE: To evaluate changes of specific retinal imaging biomarkers [intraretinal hyper-reflective retinal spots: HRS ; subfoveal neuroretinal detachment: SND; and increased foveal autofluorescence: IFAF after intravitreal steroid or anti-vascular endothelial growth factor treatment in diabetic macular oedema (DME)] as possible indicators of retinal inflammatory condition. METHODS: Retrospective analysis of images and clinical charts of 49 eyes (49 patients) with DME treated with intravitreal dexamethasone (dexamethasone, 23 eyes) or intravitreal ranibizumab (ranibizumab, 26 eyes). All patients had fundus colour photograph, spectral domain optical coherence tomography (SD OCT) and fundus autofluorescence (FAF), best-corrected visual acuity (BCVA) and microperimetry recorded before and 1 month after the end of treatment. Central macular thickness (CMT), number of HRS and presence of SND were evaluated by SD OCT. Fundus autofluorescence images were evaluated for area of (IFAF). Retinal sensitivity within 4° and 12° from fovea was quantified by microperimetry. Changes in morphologic and functional parameters were assessed, and correlation was performed by Pearson's correlation. RESULTS: Best-corrected visual acuity and CMT improved in all patients, (p < 0.05, for both groups). Mean number of HRS decreased after both treatments (p < 0.0001). Subfoveal neuroretinal detachment resolved in 85.7% dexamethasone-treated eyes (p = 0.014) and in 50% ranibizumab-treated eyes (p = 0.025). Mean IFAF area decreased in both groups, (p < 0.0001, for both). A significantly higher decrease in CMT was observed in dexamethasone- versus ranibizumab-treated eyes, (p = 0.032). In dexamethasone group, higher number of HRS at baseline and larger IFAF were correlated with higher increase in retinal sensitivity; eyes with SND at baseline had major decrease in CMT versus those without SND, (p = 0.003). CONCLUSION: Higher number of HRS, larger area of IFAF and presence of SND may indicate a prevalent inflammatory condition in DME with specific response to targeted treatment.

Microperimetry Features of Geographic Atrophy Identified With En Face Optical Coherence Tomography.

IMPORTANCE: Progressive geographic atrophy (GA) of the retinal pigment epithelium leads to loss of central vision. To identify GA in age-related macular degeneration and assess treatment, correlation of function observed on microperimetry with structure observed on optical coherence tomographic (OCT) images may be of value. OBJECTIVE: To characterize the microperimetric function of GA as identified from en face OCT imaging. DESIGN, SETTING, AND PARTICIPANTS: In a case-series study, 20 patients (22 eyes) entered the study at the University of Padova according to preplanned conditions. From March 1 to July 30, 2014, en face OCT images were obtained at the outer retinal layer and choroidal layer levels. The microperimetry sensitivity map was superimposed on the en face OCT images, which had been used to measure GA areas. Relative and dense scotoma rates were calculated in the GA areas. After data collection, the study eyes were divided into 3 groups according to the macular residual mean sensitivity. MAIN OUTCOMES AND MEASURES: Retinal sensitivity measured by microperimetry within areas of GA identified by en face OCT images. RESULTS: Twenty patients (5 men and 15 women) were included in the study, with a mean (SD) age of 79.5 (7.0) years (range, 69-98 years). Macular residual mean retinal sensitivity was less than 5 dB in 7 eyes (group 1), 5 to 10 dB in 9 eyes (group 2), and greater than 10 dB in 6 eyes (group 3). Mean (SD) GA area differed among the groups at the outer retinal (13.13 [5.03] mm2 [range, 5.75-21.04 mm2] in group 1; 7.80 [3.25] mm2 [range, 3.31-13.52 mm2] in group 2; and 3.94 [2.35] mm2 [range, 1.46-7.90 mm2] in group 3; P = .001) and choroidal (11.83 [5.55] mm2 [range, 4.55-22.14 mm2] in group 1; 7.00 [4.29] mm2 [range, 0.90-13.83 mm2] in group 2; and 3.27 [2.29] mm2 [range, 0.91-7.23 mm2] in group 3; P = .007) layer levels. Mean (SD) GA area imaged at the outer retinal layer level was significantly larger than that imaged at the choroidal level in group 3 (difference, 0.67 mm2; 95% CI, 0.31-1.03 mm2; P = .005), but not in groups 1 or 2. Mean (SD) rate of relative scotoma was significantly higher in the GA area imaged at the outer retinal layer level than at the choroidal level in group 3 (47.70% [31.30%] [range, 13.60%-100%] vs 34.00% [37.30%] [range, 0%-100%]; difference, 13.74%; 95% CI, 3.84%-23.63%; P = .02), but not in groups 1 or 2. CONCLUSIONS AND RELEVANCE: In the early stage of GA, when retinal sensitivity is relatively good, these data suggest that the GA area imaged on en face OCT at the outer retinal level correctly detects the wide functional degenerative involvement of the photoreceptors. These findings provide novel data that correlate function and structure, which may be of value when assessing treatments that might prevent or reduce the rate of growth of GA.

Rod function in diabetic patients without and with early diabetic retinopathy.

PURPOSE: To compare rod function among diabetic patients without and with mild nonproliferative diabetic retinopathy (DR) and healthy controls by means of scotopic microperimetry and dark-adapted electroretinography. METHODS: Sixty-one diabetic patients and 30 age-matched controls (control group) underwent complete ophthalmic examination, scotopic microperimetry, and dark-adapted 0.01 electroretinography (DA-ERG). RESULTS: In 32 eyes, DR was absent (no-DR group); in 29 eyes, only microaneurysms were observed (DR group). No statistically significant differences in fixation stability, fixation location, or scotopic sensitivity among the 3 groups were observed. Implicit time and amplitude of the DA-ERG b-wave of no-DR and DR groups were not different from controls. Scotopic microperimetry showed a dense scotoma centered onto the fovea in all subjects, consistent with the rod-free zone. Greater scotopic sensitivity was found in a ring located 8° from the fovea (9.33 ± 1.33 dB). CONCLUSIONS: Diabetic patients without DR and with mild nonproliferative DR did not show alterations in rod-based function, as examined by microperimetry and confirmed by DA-ERG. Scotopic microperimetry measures rod-based function and offers additional information in the evaluation of the aspects of involvement of retinal cells in diabetes.

In Vivo Detection of Choroidal Abnormalities Related to NF1: Feasibility and Comparison With Standard NIH Diagnostic Criteria in Pediatric Patients.

PURPOSE: To evaluate the feasibility of near-infrared (NIR) imaging acquisition in a large sample of consecutive pediatric patients with neurofibromatosis type 1 (NF1), to evaluate the diagnostic performance of NF1-related choroidal abnormalities as a diagnostic criterion of the disease, and to compare this criterion with other standard National Institutes of Health (NIH) diagnostic criteria. METHODS: A total of 140 consecutive pediatric patients (0-16 years old) affected by NF1 (at least two diagnostic criteria), 59 suspected (a single diagnostic criterion), and 42 healthy subjects (no diagnostic criterion) were consecutively included. Each patient underwent genetic, dermatologic, and ophthalmologic examination to evaluate the presence/absence of each NIH diagnostic criterion. The presence of NF1-related choroidal abnormalities was investigated using NIR confocal ophthalmoscopy. Two masked operators assessed Lisch nodules and NF1-related choroidal abnormalities. RESULTS: Neurofibromatosis type 1-related choroidal abnormalities were detected in 72 affected (60.5%) and 1 suspected (2.4%) child. No healthy subject had choroidal abnormalities. Feasibility rate of this sign was 82%. Sensitivity, specificity, and positive and negative predictive values of NF1-related choroidal abnormalities were 0.60, 0.97, 0.98, and 0.46, respectively. Compared with standard NIH criteria, the presence of NF1-related choroidal abnormalities was the third parameter for positive predictive value and the fourth for sensitivity, specificity, and negative predictive value. Compared with Lisch nodules, NF1-related choroidal abnormalities were characterized by higher specificity and positive predictive value. The interoperator agreement for Lisch nodules and NF1-related choroidal abnormalities was 0.67 (substantial) and 0.97 (almost perfect), respectively. The use of this sign moved one patient from the suspected to the affected group (0.5%). CONCLUSIONS: Neurofibromatosis type 1-related choroidal abnormalities represent a new diagnostic sign in NF1 children. The main advantage of this sign seems the theoretical possibility to anticipate NF1 diagnosis, whereas the main obstacle is the cooperation required by very young patients.

Progressing geographic atrophy: choroidal thickness and retinal sensitivity identify two clinical phenotypes.

PURPOSE: To analyse changes in choroidal thickness and retinal sensitivity (Se) in patients with geographic atrophy (GA) with or without choroidal neovascularisation (CNV) in the fellow eye. PARTICIPANTS: Patients with bilateral GA (B-GA group) and patients with unilateral GA and CNV in the fellow eye (U-GA group) were followed every 6 months, and enhanced depth imaging optical coherence tomography (OCT), blue and near infrared-wavelength fundus autofluorescence (B- and NIR-FAF), and microperimetry were evaluated. METHODS: GA area, choroidal thickness, and Se were measured in the eye with GA at baseline and every 6 months up to the last follow-up visit. RESULTS: 19 patients (8 in the B-GA group (16 eyes) and 11 in the U-GA group (11 eyes)) were studied. The mean±SD follow-up was 1.66±0.71 years (range 0.74-2.60 years) in the U-GA group, and 1.51±0.86 years (range 0.58-2.95 years) in the B-GA group (p=0.6766). Mean GA area was not significantly different between groups at baseline (p=0.4118 in the B-FA and p=0.6806 in the NIR-FAF) or at follow-up (p=0.5734 in the B-FAF and p=0.8945 in the NIR-FAF). Mean GA area significantly increased in both groups during follow-up (p=0.0050 for B-FAF and p=0.0052 for NIR-FAF in the U-GA group; p=0.0049 for B-FAF and p=0.0072 for NIR-FAF in the B-GA group). Choroidal thickness was significantly greater in the B-GA group compared with the U-GA group both at baseline (mean choroidal thickness 170.5±78.5 µm vs 129.1±36.1 µm; p=0.0371) and at last follow-up (173.2±86.1 µm vs 123±32.1 µm; p=0.0340). During follow-up mean choroidal thickness significantly decreased only in the U-GA group (p=0.0276); conversely mean Se significantly decreased only in B-GA group (p=0.0405). CONCLUSIONS: During follow-up, changes in Se and choroidal thickness differed in patients with GA with or without CNV in the fellow eye. These results identify at least two GA phenotypes, in which the development and progression of GA may be primarily due to different pathophysiologic mechanisms.

SUBTHRESHOLD MICROPULSE YELLOW LASER VERSUS SUBTHRESHOLD MICROPULSE INFRARED LASER IN CENTER-INVOLVING DIABETIC MACULAR EDEMA: Morphologic and Functional Safety.

BACKGROUND: To evaluate and compare in vivo retinal and choroidal morphologic changes and macular function in patients treated with yellow (Y-MPL) or infrared (IR-MPL) subthreshold micropulse laser in center-involving diabetic macular edema. METHODS: Prospective, randomized, single institution, comparative 6-month pilot study of 53 eyes (53 patients with diabetes). Inclusion criteria were previously untreated center-involving diabetic macular edema with central retinal thickness ≤400 µm (mild diabetic macular edema). Y-MPL or IR-MPL treatment was performed in a standardized pattern, using in both cases the lowest duty cycle (5%). Morphologic outcomes were the visibility of laser spots (on color fundus photographs [COL], fundus autofluorescence, fluorescein angiography, and spectral domain optical coherence tomography), retinal thickness and volume changes, foveal choroidal thickness changes, and integrity and reflectivity of the outer retinal layers. Visual function outcomes were variation in mean 4° and 12° retinal sensitivity and best-corrected visual acuity. RESULTS: Twenty-six eyes were treated with Y-MPL and 27 eyes with IR-MPL. No visible laser spots on the retina were found on COL, fundus autofluorescence, and fluorescein angiography in both treatment groups at 3 months and 6 months of follow-up. Central retinal thickness, macular volume, foveal choroidal thickness, and best-corrected visual acuity were not significantly different at any follow-up visit between the two treatment groups. There were no changes in the integrity of the external limiting membrane or inner segment/outer segment junction in both treatment groups. Mean central 4° retinal sensitivity increased in both treatment groups at 6 months (P = 0.01 and P = 0.04, respectively). Mean central 12° retinal sensitivity increased in the Y-MPL group only (P = 0.047). But, there was no significant difference in mean 4° and 12° retinal sensitivity between the 2 treatment groups at any follow-up visit. CONCLUSION: No clinically visible or invisible scars in the macula were found after Y-MPL or IR-MPL treatment. Both Y-MPL and IR-MPL with the lowest duty cycle (5%) and fixed power parameters seem to be safe from the morphologic and visual function points of view in mild center-involving diabetic macular edema.

En Face Optical Coherence Tomography to Detect and Measure Geographic Atrophy.

PURPOSE: To detect and quantify geographic atrophy (GA) secondary to age-related macular degeneration using en face optical coherence tomography (OCT) and to correlate it to GA measured with fundus autofluorescence (FAF). METHODS: Twenty-four consecutive patients (27 eyes) were studied with both standard (STD)- and enhanced depth imaging (EDI)-OCT. En face OCT images were obtained at the outer retinal layer (OR) and at the choroidal layer (CH) level for both STD- and EDI-OCT. Areas of GA were measured on the en face OCT images and were correlated with the GA areas measured on blue (B)- and near infrared (NIR)-wavelength FAF images. RESULTS: The intraoperator agreement in GA measurement was excellent with en face OCT at both OR and CH levels (intraclass correlation coefficient [ICC] = 0.99 in EDI and 0.98 in STD at OR level; 0.99 in EDI and 0.99 in STD at CH level). The interoperator agreement was excellent at OR level (ICC = 0.97 in EDI and 0.98 in STD), good at CH level (ICC = 0.95 in EDI, 0.90 in STD). The geographic atrophy area, at both B-FAF and NIR-FAF, was significantly equivalent to the GA area at OR level (B-FAF versus SDT-OR and EDI-OR: P = 0.0057 and 0.0090, respectively; NIR-FAF versus STD-OR and EDI-OR: P = 0.0131 and 0.0036, respectively), but not at CH level. CONCLUSIONS: En face OCT is a reliable method to detect and quantify GA, particularly when analyzed at the OR level, where the photoreceptors' loss creates an abrupt transition in OCT reflectivity.

Extent of diabetic macular edema by scanning laser ophthalmoscope in the retromode and its functional correlations.

BACKGROUND: To determine whether scanning laser ophthalmoscope in the retromode (RM-SLO) is useful to evaluate the extent of diabetic macular edema (DME) and its functional characteristics. METHODS: Comparative case series of 37 eyes (27 patients with diabetes). Inclusion criteria were: center involving DME determined by optical coherence tomography; RM-SLO, optical coherence tomography, fluorescein angiography (FA), and microperimetry performed on the same day; no significant media opacities. Two masked retinal specialists independently graded all images. The full extent of DME areas and two grades (small and large) DME areas were separately evaluated. The relationship between the DME extent obtained by RM-SLO and FA was assessed by Pearson correlation coefficient, intraclass correlation coefficient, and Bland-Altman plot. T-test was used to compare DME extent to central retinal thickness and macular sensitivity. RESULTS: The values of RM-SLO from the right and left prospective were highly correlated in the evaluation of the extent of DME (rho = 0.99, P < 0.0001). Mean DME area on RM-SLO was 5.7 + 5.6 mm (range, 0.3-18.2 mm); mean DME area on FA was 6.4 + 5.9 mm (range, 0.3-19.7 mm). The correlation between RM-SLO and FA in the evaluation of DME extent was highly significant (rho = 0.97, P < 0.0001), even when DME extent was divided in 2 major areas (intraclass correlation coefficient >0.8, P < 0.0001). The correlation between retinal sensitivity and DME area (RM-SLO) was significant (rho = -0.61, P = 0.0003). CONCLUSION: The extent has become an important parameter for monitoring DME, with or without treatment. The extent of DME well correlates with functional data, mainly retinal sensitivity. Retromode SLO can be reliably and easily used in the evaluation of DME extent, avoiding the use of invasive FA.

Static and dynamic retinal fixation stability in microperimetry.

OBJECTIVE: To compare static (during a pure fixation task) versus dynamic (during microperimetry) quantification of fixation stability using microperimetry in normal and pathologic eyes, by means of 2 available (clinical and bivariate contour ellipse area [BCEA]) classification methods. DESIGN: Prospective comparative observational study. PARTICIPANTS: One hundred and forty-nine eyes (110 patients) with different macular diseases and 171 normal eyes (109 subjects). METHODS: In all eyes studied, fixation stability was acquired during an isolated fixation task (static fixation) and during microperimetry (dynamic fixation). All fixation data were analyzed and compared by means of a clinical classification and by means of BCEA quantification. RESULTS: Pathologic eyes were classified as follows: 41 eyes with diabetic macular edema (DME group), 13 eyes with vitreoretinal interface disease, 60 eyes with age-related macular degeneration (AMD group), and 35 eyes with primary open-angle glaucoma. Fixation stability was not uniform among groups according to clinical classification in both static and dynamic modalities (p < 0.0001). AMD group showed larger BCEA areas compared with all other groups (p < 0.0001). All pathologic groups showed more unstable fixation in dynamic fashion according to both clinical and BCEA methods (p < 0.0001). The variation of fixation stability of control group in dynamic task was highlighted only by BCEA analysis (p < 0.0001). A deterioration of retinal fixation according to clinical method matches a significant increase in BCEA areas (p < 0.0001). CONCLUSIONS: The detection of clinical fixation stability changes improves when acquired in the dynamic modality. BCEA analysis provides more accurate evaluation of fixation stability and may detect minimal quantitative changes of the fixation area. However, a standard clinical classification can also detect changes in fixation stability in pathologic eyes. Both methods are useful tools in the evaluation of fixation stability.

Microperimetry, fundus autofluorescence, and retinal layer changes in progressing geographic atrophy.

OBJECTIVE: To analyze correlation among microperimetry, inner and outer retinal layers, and fundus autofluorescence (FAF) changes in eyes with progressing geographic atrophy (GA) secondary to age-related macular degeneration. METHODS: Microperimetry, spectral-domain optical coherence tomography (SD-OCT), standard short-wavelength FAF (SW-FAF), and near-infrared-wavelength FAF (NIR-FAF) were performed for all patients at both baseline and follow-up visits. FAF pattern, integrity of photoreceptor inner segment/outer segment (IS/OS) junction, total retinal thickness (RT), inner retinal layers (IRL), and outer retinal layers (ORL) thickness changes of every microperimetry extrafoveal tested point were analyzed. RESULTS: A total of 366 microperimetry tested points were analyzed (6 patients, 7 eyes). Mean retinal sensitivity significantly decreased (p = 0.0149), and the percentage of dense scotomas significantly increased (p = 0.0125). Mean RT and mean ORL thickness significantly decreased (both p < 0.0001). Mean IRL thickness significantly increased (p = 0.0001). The decrease of ORL thickness was inversely correlated to the IRL thinning (rho = -0.710). FAF pattern at baseline was correlated to RT and ORL thickness (both p < 0.0001) and was significantly correlated to the risk to evolve to dense scotoma during follow-up (p = 0.0001 at SW-FAF, p < 0.0001 at NIR-FAF). Tested points showing at baseline the loss of photoreceptor IS/OS junction had a greater risk for evolving to dense scotoma compared with those with intact photoreceptor IS/OS junction (odds ratio 3.56, 95% CI 2.41-5.27). CONCLUSIONS: Retinal sensitivity changes are correlated to IRL and ORL thickness changes, and to photoreceptor IS/OS junction integrity. FAF patterns remain a relevant factor in predicting GA evolution. Microperimetry, SW-FAF and NIR-FAF, and SD-OCT should be combined to obtain adequate morphologic and functional prospective information.

Subthreshold laser therapy for diabetic macular edema: metabolic and safety issues.

PURPOSE: To review the most important metabolic effects and clinical safety data of subthreshold micropulse diode laser (D-MPL) in diabetic macular edema (DME). METHODS: Review of the literature about the mechanisms of action and role of D-MPL in DME. RESULTS: The MPL treatment does not damage the retina and is selectively absorbed by the retinal pigment epithelium (RPE). MPL stimulates secretion of different protective cytokines by the RPE. No visible laser spots on the retina were noted on any fundus image modality in different studies, and there were no changes of the outer retina integrity. Mean central retinal sensitivity (RS) increased in subthreshold micropulse diode laser group compared to standard ETDRS photocoagulation group. CONCLUSIONS: MPL is a new, promising treatment option in DME, with both infrared and yellow wavelengths using the less aggressive duty cycle (5%) and fixed power parameters. It appears to be safe from morphologic and functional point of view in mild center involving DME.