An Automated Comparative Analysis of the Exudative Biomarkers in Neovascular Age-Related Macular Degeneration, The RAP Study: Report 6.

PURPOSE: To investigate differences in volume and distribution of the main exudative biomarkers across all types and subtypes of macular neovascularization (MNV) using artificial intelligence (AI). DESIGN: Cross-sectional study. METHODS: An AI-based analysis was conducted on 34,528 OCT B-scans consisting of 281 (250 unifocal, 31 multifocal) MNV3, 55 MNV2, and 121 (30 polypoidal, 91 non-polypoidal) MNV1 treatment-naive eyes. Means (SDs), medians and heat maps of cystic intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachments (PED), and hyperreflective foci (HRF) volumes, as well as retinal thickness (RT) were compared among MNV types and subtypes. RESULTS: MNV3 had the highest mean IRF with 291 (290) nL, RT with 357 (49) µm, and HRF with 80 (70) nL, P ≤ .05. MNV1 showed the greatest mean SRF with 492 (586) nL, whereas MNV3 exhibited the lowest with 218 (382) nL, P ≤ .05. Heat maps showed IRF confined to the center, whereas SRF was scattered in all types. SRF, HRF, and PED were more distributed in the temporal macular half in MNV3. Means of IRF, HRF, and PED were higher in the multifocal than in the unifocal MNV3 with 416 (309) nL,114 (95) nL, and 810 (850) nL, P ≤ .05. Compared to the non-polypoidal subtype, the polypoidal subtype had greater means of SRF with 695 (718) nL, HRF 69 (63) nL, RT 357 (45) µm, and PED 1115 (1170) nL, P ≤ .05. CONCLUSIONS: This novel quantitative AI analysis shows that SRF is a biomarker of choroidal origin in MNV1, whereas IRF, HRF, and RT are retinal biomarkers in MNV3. Polypoidal MNV1 and multifocal MNV3 present with higher exudation compared to other subtypes.

THE IMPACT OF THE VITREOMACULAR INTERFACE ON FUNCTIONAL AND ANATOMICAL OUTCOMES IN DIABETIC MACULAR EDEMA TREATED WITH THREE DIFFERENT ANTI-VEGF AGENTS: Post Hoc Analysis of The Protocol T Study.

PURPOSE: To investigate the impact of baseline vitreomacular interface status on treatment outcomes in patients treated with three different anti-vascular endothelial growth factors for diabetic macular edema. METHODS: Post hoc analysis from patients enrolled in the DRCR.net Protocol T study. Optical coherence tomography images were analyzed at baseline and at the end of follow-up to identify the presence of complete vitreomacular adhesion, partial vitreomacular adhesion, vitreomacular traction syndrome, and complete posterior vitreous detachment. RESULTS: Six hundred and twenty-nine eyes were eligible for the study based on the study criteria. Complete adhesion eyes gained on average +3.7 more ETDRS letters compared with the complete posterior vitreous detachment group at the end of the 12 months follow-up ( P < 0.001). Baseline vitreomacular interface status had no significant influence on central subfield thickness at 12 months ( P = 0.144). There was no difference between the treatment arms based on effect of baseline vitreomacular interface status on best-corrected visual acuity gain. CONCLUSION: This study provides evidence that vitreomacular interface status affects functional outcomes in diabetic macular edema patients treated with anti-vascular endothelial growth factor injections. The presence of complete or partial vitreomacular adhesion at baseline may be associated with a larger treatment benefit than those with complete posterior vitreous detachment.

THE RAP STUDY, REPORT 5: REDISCOVERING MACULAR NEOVASCULARIZATION TYPE 3: Multimodal Imaging of Fellow Eyes over 24 months.

PURPOSE: To explore the condition of fellow eyes of patients with macular neovascularization Type 3 (MNV3) and to verify whether the retinal-choroidal anastomosis (RCA) develops equally in all MNV types. METHODS: The contralateral eyes of 94 patients with MNV3, 96 patients with MNV1, and 96 patients with MNV2 were included. Multimodal imaging was performed. The MNV3 stage including the development of fibrosis and RCA over 24 months was determined. RESULTS: In the contralateral eyes of patients of the solitary (one lesion) MNV3 group, 32 eyes (42.1%) showed early/intermediate age-related macular degeneration, 25 eyes (33%) showed MNV3, and 11 eyes (14.5%) experienced fibrosis, of which 4 eyes (5.2%) had a RCA, 7 eyes (9.2%) had atrophy after resolved MNV3, and 1 eye (1.3%) developed MNV1. In the multifocal (more than one lesion) MNV3 group, 2 eyes (11.1%) showed early/intermediate age-related macular degeneration, 9 eyes (50%) showed 15 MNV3 lesions, and 4 eyes (22.2%) showed fibrosis, of which 2 eyes (11.1%) manifested with a RCA and 3 eyes (16.7%) showed atrophy after resolved MNV3. The number of eyes with a RCA accounted for 40% of all eyes with fibrosis. The count of simultaneous bilateral multifocal MNV3 was 5 (55.6%). In the MNV1 and MNV2 groups, no eye developed a RCA. The incidence of RCAs in the scarred eyes in MNV3 was significantly higher (P < 0.0001). CONCLUSION: Retinal-choroidal anastomosis is an exclusive clinical feature of MNV3. The development of the multifocal MNV3 is usually bilateral and simultaneous. The occurrence of fibrosis in MNV3 has decreased dramatically after the introduction of the antiangiogenic therapy.

The RAP study, report 3: Discoloration of the macular region in patients with macular neovascularization type 3.

BACKGROUND/AIMS: To explore whether the existence and pattern of distribution of macular haemorrhage or exudate can be valuable diagnostic markers for macular neovascularization type 3 (MNV3) in patients with neovascular age-related macular degeneration. METHODS: Eighty-three eyes of 83 consecutive treatment naïve patients with stage 3 MNV3 were enrolled. The diagnosis was based on fluorescein angiography (FA) and optical coherence tomography (OCT). Subretinal and intraretinal haemorrhage and dense exudates were evaluated on colour fundus photography. Fluorescein angiography (FA) images and OCT scans were used to identify the axial location of the haemorrhage. 83 patients with MNV1 and 83 with MNV2 were included as two control groups. RESULTS: In the MNV3 group, 62 (75%) eyes had intraretinal haemorrhage and 52 (63%) had dense exudates. 73 (88%) eyes had intraretinal haemorrhage and/or dense exudates. 41 (49%) had both pathologies. The intraretinal haemorrhage was flame shaped over the lesion and punctate or semi-punctate further away from it and directed to the fovea. No subretinal haemorrhage was noticed. In the MNV1 and MNV2 groups, 11 (13%) and 24 (29%) eyes had subretinal haemorrhage or dense exudates, respectively. No intraretinal haemorrhage was seen in the two control groups. The prevalence of exudates and haemorrhage (irrespective of its location) was greater in MNV3 than in MNV1 or 2 (p < 0.0001). CONCLUSION: The existence and pattern of distribution of intraretinal haemorrhage is pathognomonic of MNV3. It makes (alone or with dense exudates) the diagnose MNV3 possible using fundoscopy or colour fundus photo and without further diagnostic expenditure.

Macular Telangiectasia type 2: multimodal assessment of retinal function and microstructure.

PURPOSE: To assess the impact of neurodegenerative morphologic alterations due to macular telangiectasia type 2 (MacTel) on microperimetry (MP) and multifocal electroretinography (mfERG). METHODS: Thirty-five eyes of 18 patients with MacTel were examined using spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), mfERG and MP. Software was used to match SD-OCT B-scans with the corresponding retinal sensitivity map and multifocal electroretinograms (mfERGs), thus enabling direct structure/function correlation. RESULTS: Loss of the ellipsoid zone (EZ) had the strongest negative association with retinal sensitivity (16.77 dB versus 4.58 dB, adj. p < 0.001) of all parameters examined, and a limited negative effect on mfERGs (0.32 SD versus -1.97 SD adj. p = 0.121). Ellipsoid zone (EZ) irregularity was associated with reduced MP values but preserved mfERGs. There was a significant association between areas of inner retinal hyporeflectivity and loss of MP sensitivity (adj. p < 0.001) but the reduction in sensitivity was less than in locations with EZ loss. Areas of mfERG abnormality showed similar sensitivity loss with either inner retinal hyporeflectivity or EZ loss (adj. p = 0.063). In areas with EZ loss alone, preservation of the external limiting membrane (ELM) was associated with higher MP values than in areas with additional ELM loss; the integrity of the ELM alone was not associated with changes either in MP or mfERG. Increased FAF was observed in 51% of eyes, mixed/reduced FAF in 40%, and no abnormality was detected in 9% of eyes. CONCLUSION: The data suggest both MP and mfERG to be useful non-invasive modalities for detecting localised macular dysfunction in MacTel. The findings suggest a different sensitivity of the two modalities to inner and outer retinal changes in macular function and are therefore complementary.

The RAP study, report 4: morphological and topographical characteristics of multifocal macular neovascularization type 3.

PURPOSE: To report on the morphological characteristics and regional distribution of multifocal macular neovascularization type 3 (mMNV3). METHODS: Twenty-two consecutive eyes of 21 patients with mMNV3 were included using multimodal imaging. The count and stage of lesions of all MNV types and the existence of exudate and hemorrhage were determined. Also, we addressed the regional distribution of MNV3 lesions between the superior-inferior and the nasal-temporal halves of the macula, and the range of the distance of the lesions from the central fovea. Furthermore, we explored the number of feeding vessels including the cilioretinal artery. RESULTS: We found 51 lesions in 22 eyes of 21 patients. They were bifocal in 16 (73%) eyes, trifocal in 5 (23%), and quadrifocal in one (4%). No lesion of MNV1 or 2 was found. Fifteen (68%), 2 (9%), and 16 (73%) eyes were associated with retinal hard exudate, subretinal pigment epithelium exudate, and intraretinal hemorrhage, respectively. Thirty (59%) lesions were located in the temporal half of the macula, whereas 21 (41%) were located nasally (p = 0.07). One (2%) lesion was closer than 500 µm, 49 (96%) between 500 and 1500 µm, and one (2%) between 1500 and 3000 µm. The lesions were supplied by one arteriole in one (4%) eye, two arterioles in 16 (73%) eyes, and 3 arterioles in 5 (23%) eyes. The CRA contributed as a feeding vessel in 5 (23%) eyes. CONCLUSION: The multifocal variant of MNV3 has specific morphological and topographical characteristics. Multimodal imaging allows the understanding of the pathomorphological condition in more detail.

CYSTOID MACULAR EDEMA IN THE SETTING OF PRIMARY VITREORETINAL LYMPHOMA.

PURPOSE: To present a rare case of primary vitreoretinal lymphoma presenting with cystoid macular edema without previous surgical intervention or radiotherapy. METHODS: Retrospective chart review of one patient. RESULTS: A 74-year-old patient was seen with a history of cataract surgery in 1 eye and presumed ocular inflammation with recurrent cystoid macular edema in both eyes. On examination, subretinal pigment epithelial and intraretinal infiltrates raised the suspicion of primary vitreoretinal lymphoma despite the unusual presentation with cystoid macular edema. A magnetic resonance imaging and brain biopsy confirmed the diagnosis of vitreoretinal lymphoma in the setting of central nervous system lymphoma. CONCLUSION: Primary vitreoretinal lymphoma can present with cystoid macular edema in rare cases.

RAP study, report 1: novel subtype of macular neovascularisation type III, cilioretinal MNV3.

PURPOSE: To report on patients with macular neovascularisation type III (MNV3) arising from cilioretinal arteries (CRAs) (cilioretinal macular neovascularisation type III (cMNV3)). METHODS: We reviewed baseline examinations of patients with neovascular age-related macular degeneration using multimodal imaging. We determined the type and distribution of MNV lesions in each cMNV3 case, the range of distances from the fovea, existence of exudative maculopathy, intraretinal haemorrhage and other morphological characteristics. 50 consecutive eyes with usual MNV3 without CRA were included as a control group. RESULTS: 102 eyes of 102 patients were identified with MNV3 lesions. Among these, we found 12 eyes (12%) with cMNV3, 84 eyes (82%) with usual MNV3 without CRA and 6 eyes (6%) with usual MNV3 with CRA. Ten cases of cMNV3 had one lesion, and two cases had two lesions. The lesions were distributed equally between the superior and inferior halves of the macula, whereas in the nasal and temporal halves, there were 8 (57%) and 6 (43%) lesions, respectively. All cMNV3 lesions were located between 500 and 1500 µm from the central fovea except one, which was located between 1500 and 3000 µm. None of the lesions had macular neovascularisation type I (MNV1) or macular neovascularisation type II (MNV2) elsewhere in both groups. Exudative maculopathy and intraretinal haemorrhage were found in seven (88%) and five (63%) of the eight pure cMNV3 cases, respectively. CONCLUSION: cMNV3 can be solitary or multiple, isolated or accompanied with usual MNV3 lesions, but not with concurrent MNV1 or MNV2. It is frequently associated with extensive exudative maculopathy, intraretinal haemorrhage and subretinal fluid.

IMAGING OF VITELLIFORM MACULAR LESIONS USING POLARIZATION-SENSITIVE OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To examine the involvement of the retinal pigment epithelium (RPE) in the presence of vitelliform macular lesions (VML) in Best vitelliform macular dystrophy (BVMD), autosomal recessive bestrophinopathy, and adult-onset vitelliform macular degeneration using polarization-sensitive optical coherence tomography (PS-OCT). METHODS: A total of 35 eyes of 18 patients were imaged using a PS-OCT system and blue light fundus autofluorescence imaging. Pathogenic mutations in the BEST1 gene, 3 of which were new, were detected in all patients with BVMD and autosomal recessive bestrophinopathy. RESULTS: Polarization-sensitive optical coherence tomography showed a characteristic pattern in all three diseases with nondepolarizing material in the subretinal space consistent with the yellowish VML seen on funduscopy with a visible RPE line below it. A focal RPE thickening was seen in 26 eyes under or at the edge of the VML. Retinal pigment epithelium thickness outside the VML was normal or mildly thinned in patients with BVMD and adult-onset vitelliform macular degeneration but was diffusely thinned or atrophic in patients with autosomal recessive bestrophinopathy. Patients with autosomal recessive bestrophinopathy showed sub-RPE fibrosis alongside the subretinal VML. Polarization-sensitive optical coherence tomography was more reliable in assessing the localization and the integrity of the RPE than spectral domain OCT alone. On spectral domain OCT, identification of the RPE was not possible in 19.4% of eyes. Polarization-sensitive optical coherence tomography allowed for definite identification of the location of VML in respect to the RPE in all eyes, since it provides a tissue-specific contrast. CONCLUSION: Polarization-sensitive optical coherence tomography confirms in vivo the subretinal location of VML and is useful in the assessment of RPE integrity.

Association of Changes in Macular Perfusion With Ranibizumab Treatment for Diabetic Macular Edema: A Subanalysis of the RESTORE (Extension) Study.

Importance: Anti-vascular endothelial growth factor treatment is the first-line therapy in the treatment of center-involving diabetic macular edema. Data on capillary perfusion changes under repeated treatment in a possibly compromised vascular network are limited. Objective: To evaluate the association of repeated ranibizumab injections on macular perfusion in patients with diabetic macular edema. Design, Setting, and Participants: This study analyzed prospectively collected data from the 12-month RESTORE core study and the 24-month open label RESTORE extension study, which assessed the efficacy and safety of ranibizumab in patients with visual impairment due to diabetic macular edema. Of 345 patients with center-involving diabetic macular edema who had enrolled in the 12-month RESTORE core study, 240 entered the 24-month RESTORE extension study. Of these, 83 (34.6%) received ranibizumab, 83 (34.6%) received ranibizumab and laser combination therapy, and 74 (30.8%) received laser monotherapy in the first year of the study; 208 completed the 24-month extension study. Fluorescence angiography images were taken from each participant twice each year graded by Vienna Reading Center on severity of capillary loss in the parafoveal area, regularity of the foveal avascular zone outline, and measurement of the size of the foveal avascular zone, following a standardized protocol. Data analysis took place from July 2014 through December 2017. Main Outcomes and Measures: Change in 3 fluorescence angiography perfusion parameters over the course of treatment. Results: Mean (SD) patient age was 62.6 (8.8) years; 124 of 208 (59.2%) were male and 197 of 208 (94.6%) were white. The number of patients with definite altered foveal avascular zone regularity at baseline was 103 of 240 patients (42.9%); another 118 patients (49.2%) had questionably altered regularity at baseline. Definitive capillary loss was found in 65 of 240 patients (27.1%) at baseline. Mean (SD) foveal avascular zone size at baseline was 0.261 (0.232) mm2 in ranibizumab monotherapy, 0.231 (0.219) mm2 in ranibizumab and macular laser combination therapy, and 0.201 (0.13) mm2 in laser monotherapy. No treatment arm experienced significant increase in foveal avascular zone size at any time in the study period. At month 36, ranibizumab monotherapy resulted in a mean increase of 0.073 mm2 (95% CI, 0.005-0.142 mm2) and combination therapy resulted in a mean increase of 0.117 mm2 (95% CI, 0.045-0.188 mm2), but no changes were statistically significant. No changes occurred in foveal avascular zone regularity in any treatment group, and no differences were found in capillary loss around the fovea in the 3 treatment groups; neither element could be correlated with visual acuity or central retinal thickness. Conclusions and Relevance: Repeated ranibizumab treatment was not associated with impaired macular perfusion in our study cohort. Because our data do not suggest a harmful effect of anti-vascular endothelial growth factor therapy on capillary integrity, patients with severe microangiopathy and advanced capillary dropout should not be denied these treatments.

Intraretinal cysts are the most relevant prognostic biomarker in neovascular age-related macular degeneration independent of the therapeutic strategy.

BACKGROUND/AIMS: To investigate the impact of antiangiogenic monotherapy and photodynamic therapy (PDT) as add-on strategy on retinal morphology, and to analyse prognostic biomarkers for visual outcome and retreatment frequency in neovascular age-related macular degeneration (nAMD). METHODS: 255 patients participating in the MONT BLANC study were evaluated. Patients were randomised to receive as-needed ranibizumab monotherapy or combination therapy (verteporfin PDT and ranibizumab). Outcome measures included visual acuity (VA), retinal morphology assessed by optical coherence tomography and retreatment frequency. RESULTS: The proportion of scans showing intraretinal cysts (IRC) or subretinal fluid (SRF) decreased more intensively in the combination than in the monotherapy group. Pigment epithelial detachments (PED) decreased significantly only in the combination group. Patients with IRC presented the lowest initial VA, and IRC had the strongest negative predictive value for functional improvement in both groups. SRF showed a predictive value for a higher number of ranibizumab injections (combination, +0.9; monotherapy, +0.8) and a higher number of PDT treatments in the combination group (+0.3). PED was associated with a higher number of ranibizumab injections only in the monotherapy group (+1.2). CONCLUSIONS: Combination and monotherapy showed a distinct response pattern for morphological parameters in nAMD. IRC was the only relevant prognostic parameter for functional outcome. TRIAL REGISTRATION NUMBER: NCT00433017.

Morphologic parameters relevant for visual outcome during anti-angiogenic therapy of neovascular age-related macular degeneration.

PURPOSE: To identify the effects of anti-angiogenic therapy in neovascular age-related macular degeneration (AMD) in respect to morphologic type and time course and to identify prognostic factors for visual outcome on the basis of standardized optical coherence tomography (OCT) analysis. DESIGN: Subanalysis of a prospective, 12-month, multicenter, phase IIIb trial (Efficacy and Safety of Ranibizumab in Patients with Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration [EXCITE]). PARTICIPANTS: A total of 353 treatment-naïve patients with subfoveal choroidal neovascularization (CNV) receiving quarterly or monthly ranibizumab therapy. METHODS: Patients were randomized to receive 0.3 mg quarterly, 0.5 mg quarterly, or 0.3 mg monthly doses of ranibizumab. Treatment comprised a loading phase of 3 consecutive monthly injections followed by a 9-month maintenance phase of monthly or quarterly injections. Best-corrected visual acuity (BCVA) was measured using the Early Treatment Diabetic Retinopathy Study protocol, and retinal morphology was assessed by Stratus OCT (Carl Zeiss Meditec, Dublin, CA). Imaging data were evaluated by certified examiners of the Vienna Reading Center using a standardized protocol. MAIN OUTCOME MEASURES: The BCVA was measured using ETDRS charts and retinal morphology was assessed by OCT. RESULTS: During the loading phase, there was a significant correlation between a reduction in central retinal thickness and an increase in BCVA (P < 0.001), which decreased during the maintenance phase in all treatment arms. The proportion of patients showing retinal morphologic changes, such as intraretinal cysts (IRCs), subretinal fluid (SRF), and pigment epithelial detachments (PEDs), decreased significantly in all groups (P < 0.001), more intensively in the 0.5 mg quarterly than in both 0.3 mg groups. Intraretinal cysts resolved most rapidly followed by SRF, whereas PED decreased at a slower rate and intensity. Patients with IRC at baseline had lower BCVA levels that remained lower over the entire study period, whereas recurrence of IRC during follow-up showed no additional negative effect on function. Baseline SRF had no effect on visual recovery; however, recurrence of SRF during follow-up showed a tendency for an additional negative effect on function (P = 0.06). Baseline PED showed a negative influence on visual outcome only in combination with IRC and SRF. CONCLUSIONS: There is a distinct response pattern and time course of morphologic parameters associated with anti-vascular endothelial growth factor therapy in neovascular AMD. Specific alterations, such as IRC, SRF, and PED, as baseline or follow-up features are significantly influencing the potential for visual gain.

Refractive changes after pharmacologic resolution of diabetic macular edema.

PURPOSE: To determine precisely the mean change in refractive power induced by treatment in patients with diabetic macular edema (DME). DESIGN: Prospective, randomized study. PARTICIPANTS: Fifty eyes of 50 consecutive patients with clinically significant macular edema receiving all 3 types of current state-of-the-art treatment with intravitreal antiedematous substances (ranibizumab, bevacizumab, or triamcinolone). METHODS: Patients were followed up at monthly intervals and were treated following a standardized pro re nata regimen according to protocol. Best-corrected visual acuity (BCVA) was determined by certified visual acuity examiners. The refractive power of the treated eyes was determined using a push-plus technique. The change in refraction between baseline and the visit when the macula was completely dry or when the central subfield thickness (CST) measured by optical coherence tomography had reached the thinnest level was analyzed. MAIN OUTCOME MEASURES: Spherical equivalent refraction (SER) and CST. RESULTS: Fifty eyes of 50 patients received intravitreal therapy using ranibizumab (n = 11), bevacizumab (n = 20), or triamcinolone (n = 19). Mean BCVA was 0.33±0.23 logarithm of the minimum angle of resolution (logMAR) and mean CST was 492±130 µm. The mean SER was 0.41±2.06 diopters (D) at baseline. The BCVA at the time of optimal retinal morphologic features was 0.24±0.2 logMAR, mean CST was 300±78 µm, and mean change in SER was -0.01±0.46 D. Changes is BCVA and CST were statistically significant (P < 0.0001), but the SER change was not (P = 0.824). CONCLUSIONS: Appropriate spectacle correction can be prescribed to patients with DME any time during ongoing therapy using antiedematous substances because resolution of retinal thickening is not associated with an increased risk of a myopic shift.

Characterization of stargardt disease using polarization-sensitive optical coherence tomography and fundus autofluorescence imaging.

PURPOSE: To identify disease-specific changes in Stargardt disease (STGD) based on imaging with polarization-sensitive spectral-domain optical coherence tomography (PS-OCT) and to compare structural changes with those visible on blue light fundus autofluorescence (FAF) imaging. METHODS: Twenty-eight eyes of 14 patients diagnosed with STGD were imaged using a novel high-speed, large-field PS-OCT system and FAF (excitation 488 nm, emission > 500 nm). The ophthalmoscopic phenotype was classified into three groups. ABCA4 mutation testing detected 15 STGD alleles, six of which harbor novel mutations. RESULTS: STGD phenotype 1 (12 eyes) showed sharply delineated areas of absent RPE signal on RPE segmentation B-scans of PS-OCT correlating with areas of hypofluorescence on FAF. Adjacent areas of irregular fluorescence correlated with an irregular RPE segmentation line with absence of overlaying photoreceptor layers. Eyes characterized on OCT by a gap in the subfoveal outer segment layer (foveal cavitation) showed a normal RPE segmentation line on PS-OCT. Hyperfluorescent flecks on FAF in phenotype 2 STGD (8 eyes) were identified as clusters of depolarizing material at the level of the RPE. Distribution of flecks could be depicted on RPE elevation maps. An increased amount of depolarizing material in the choroid was characteristic for STGD Phenotype 3 (8 eyes). CONCLUSIONS: PS-OCT together with FAF identified characteristic patterns of changes in different stages of the disease. PS-OCT is a promising new tool for diagnosis and evaluation of future treatment modalities in STGD.

In vivo identification of alteration of inner neurosensory layers in branch retinal artery occlusion.

BACKGROUND/AIMS: To characterise the extension and progression of alteration of neurosensory layers following acute and chronic branch retinal artery occlusion (BRAO) in vivo using spectral-domain optical coherence tomography. METHODS: In this observational case series, eight eyes with acute BRAO and nine eyes with chronic BRAO were analysed using a Spectralis Heidelberg Retina Angiograph (HRA)+optical coherence tomography system including eye tracking. Patients with acute BRAO were examined within 36±5 h after primary event and at weekly/monthly intervals thereafter. Segmentation measurements of all individual neurosensory layers were performed on single A-scans at six locations in affected and corresponding non-affected areas. The thickness values of the retinal nerve fibre layer together with the ganglion cell layer (NFL/GCL), inner plexiform layer (IPL), inner nuclear layer together with outer plexiform layer (INL/OPL), outer nuclear layer (ONL), and photoreceptor layers together with the retinal pigment epithelium (PR/RPE) were measured and analysed. RESULTS: Segmentation evaluation revealed a distinct increase in thickness of inner neurosensory layers including the NFL/GCL (35%), IPL (80%), INL/OPL (48%) and mildly the ONL by 21% in acute ischaemia compared with corresponding layers in non-ischaemic areas. Regression of intraretinal oedema was followed by persistent retinal atrophy with loss of differentiation between IPL and INL/OPL at month 2. In contrast, the ONL and subjacent PR/RPE retained their physiological thickness in patients with chronic BRAO. CONCLUSION: In vivo assessment of retinal layer morphology allows a precise identification of the pathophysiology in retinal ischaemia.

Evaluation of optical coherence tomography findings in age-related macular degeneration: a reproducibility study of two independent reading centres.

BACKGROUND/AIMS: To determine the reproducibility among readers of two independent certified centres, the Vienna Reading Center (VRC) and the University of Wisconsin-Madison Reading Center (UW-FPRC) for optical coherence tomography (OCT) images in age-related macular degeneration (AMD). METHODS: Fast macular thickness scans and 6 mm cross hair scans were obtained from 100 eyes with all subtypes of AMD using Stratus OCT. Consensus readings were performed by two certified OCT readers of each reading center using their grading protocol. Common variables of both grading protocols, such as presence of cystoid spaces, subretinal fluid, vitreomacular traction and retinal pigment epithelial detachment, were compared using κ statistics. In addition, the intraclass correlation coefficient (ICC) was calculated for centre point thickness (CPT) of values re-measured manually in the presence of alignment errors. RESULTS: The reproducibility was dependent on the variable measured with a κ value of 0.81 for the presence of cystoid spaces, 0.78 for the presence of subretinal fluid and 0.795 for the presence of vitreomacular traction. The lowest reproducibility was found for the presence of retinal pigment epithelial detachment with a κ value of 0.51. The CPT was re-measured in 29 out of 100 scans at both sites with an ICC of the re-measured thicknesses of 0.92. CONCLUSION: OCT scan data are crucial in monitoring treatment efficacy in AMD clinical trials. For comparison of results obtained by different reading centers, the inter-reading center reproducibility is essential. Although the reproducibility is generally high, the reliability depends on the selected morphological parameters.

High-resolution imaging of the human retina in vivo after scatter photocoagulation treatment using a semiautomated laser system.

PURPOSE: To image the ultrastructural morphology of retinal laser effects and their healing response in vivo using spectral domain optical coherence tomography (SD-OCT). DESIGN: Prospective, interventional study. PARTICIPANTS: Ten patients undergoing panretinal photocoagulation for proliferative diabetic retinopathy. METHODS: Panretinal photocoagulation (PRP) was performed using a semiautomated patterned scanning laser system providing a raster of effects with homogenous intensity. Retinal morphology and localization of effects owing to laser-tissue interaction were imaged at 1 day, 1 week, and at monthly intervals for 6 months. The characteristic, specific structural changes during the healing process were followed over time using an SD-OCT device (Spectralis OCT) allowing for high-resolution raster scanning of the entire lesion pattern with identification of identical retinal sites (tracking modality). MAIN OUTCOME MEASURES: Retinal morphology and localization of effects of photocoagulation on SD-OCT images. RESULTS: At day 1 after PRP, the photocoagulation effects were sharply delineated from the surrounding unaffected retina and all spots seemed to be identical in size and location. The area of tissue destruction was confined to the outer retinal layers, extending from the outer nuclear layer (ONL) to the retinal pigment epithelium (RPE). At 1 week, images showed a progressive loss of the affected outer retinal layers, namely, the ONL and the outer plexiform layer. Concomitant distortion of the inner nuclear and plexiform layers generated a pattern of "archways" between adjacent laser spots. The photoreceptor layers (PRL) seemed to be eliminated in the photocoagulated area, particularly at the borders of each lesion. The lesion center contained a condensed RPE and PRL segment. The ONL recovered partially, but the PRL inner and outer segments remained absent. During the long-term follow-up, RPE cells migrated to the center of the lesion, forming a hyperplastic scar. CONCLUSIONS: The characteristic morphology of retinal photocoagulation effects in vivo and over time was identified for the first time in human eyes using SD-OCT. The OCT imaging demonstrated a well-defined reproducible area of destruction confined to the outer retinal layers. Healing proceeded as the condensation of the RPE and PRL in the lesion center.