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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.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.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 (P0.0001).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.

To investigate the correlation of volumetric measurements of intraretinal (IRF) and subretinal fluid obtained by deep learning and central retinal subfield thickness (CSFT) based on optical coherence tomography in retinal vein occlusion, diabetic macular edema, and neovascular age-related macular degeneration.A previously validated deep learning-based approach was used for automated segmentation of IRF and subretinal fluid in spectral domain optical coherence tomography images. Optical coherence tomography volumes of 2.433 patients obtained from multicenter studies were analyzed. Fluid volumes were measured at baseline and under antivascular endothelial growth factor therapy in the central 1, 3, and 6 mm.Patients with neovascular age-related macular degeneration generally demonstrated the weakest association between CSFT and fluid volume measurements in the central 1 mm (0.107-0.569). In patients with diabetic macular edema, IRF correlated moderately with CSFT (0.668-0.797). In patients with retinal vein occlusion, IRF volumes showed a moderate correlation with CSFT (0.603-0.704).The correlation of CSFT and fluid volumes depends on the underlying pathology. Although the amount of central IRF seems to partly drive CSFT in diabetic macular edema and retinal vein occlusion, it has only a limited impact on patients with neovascular age-related macular degeneration. Our findings do not support the use of CSFT as a primary or secondary outcome measure for the quantification of exudative activity or treatment guidance.

To characterize the spectrum of internal limiting membrane (ILM) disease in Alport syndrome using multimodal imaging, including widefield (WF) and ultra-widefield (UWF) modalities, and to report their relative prevalence according to the genetic pattern of inheritance.Cross-sectional clinical study of patients diagnosed with Alport syndrome. All patients underwent UWF color photography and autofluorescence, WF-optical coherence tomography angiography and spectral-domain optical coherence tomography. Demographics, past medical and ophthalmic history, and genetic mutation history were collected.Forty-two eyes of 21 patients (11 men; age 36.6 ± 12.9 years) were included. Macular spectral-domain optical coherence tomography revealed ILM granularity, more frequent in X-linked Alport syndrome and corresponding to dot maculopathy on color fundus. Mid-peripheral spectral-domain optical coherence tomography scans revealed multilamellated ILM in eight eyes (19%), presumably progressive, which corresponded to a cavitary pattern on en-face OCT. En-face OCT revealed multiple areas of retinal nerve fiber layer dehiscence in the macula, overlapping with vascular lacunae on optical coherence tomography angiography, and a coarse arrangement of retinal nerve fiber layer above and below the temporal raphe in 20 eyes (52%).Multimodal imaging allowed for the detection/characterization of retinal findings (ILM granularity, progressive ILM lamellation, retinal nerve fiber layer dehiscence, vascular lacunae, and coarse arrangement of retinal nerve fiber layer toward the disc) as multifaceted manifestations of ILM disease in Alport syndrome.

To investigate associations between residual subretinal fluid (rSRF) volumes, quantified using artificial intelligence and treatment outcomes in a subretinal fluid (SRF)-tolerant treat-and-extend (TE) regimen in neovascular age-related macular degeneration.Patients enrolled in the prospective, multicenter FLUID study randomized in an SRF-tolerant TE regimen were examined by spectral-domain optical coherence tomography and tested for best-corrected visual acuity (BCVA). Intraretinal fluid and SRF volumes were quantified using artificial intelligence tools. In total, 375 visits of 98 patients were divided into subgroups: extended intervals despite rSRF and extended intervals without fluid. Associations between BCVA change, SRF volume, subgroups, and treatment intervals were estimated using linear mixed models.In extended intervals despite rSRF, increased SRF was associated with reduced BCVA at the next visit in the central 1 mm (-0.138 letters per nL; P = 0.014) and 6 mm (-0.024 letters per nL; P = 0.049). A negative association between increased interval and BCVA change was found for rSRF in 1 mm and 6 mm (-0.250 and -0.233 letter per week interval, respectively; both P0.001). Extended intervals despite rSRF had significantly higher SRF volumes in the central 6 mm at the following visit (P = 0.002).Artificial intelligence-based analysis of extended visits despite rSRF demonstrated increasing SRF volumes associated with BCVA loss at the consecutive visit. This negative association contributes to the understanding of rSRF volumes on treatment outcomes in neovascular age-related macular degeneration.

PURPOSE: To investigate quantitative differences in fluid volumes between subretinal fluid (SRF)-tolerant and SRF-intolerant treat-and-extend regimens for neovascular age-related macular degeneration and analyze the association with best-corrected visual acuity. METHODS: Macular fluid (SRF and intraretinal fluid) was quantified on optical coherence tomography volumetric scans using a trained and validated deep learning algorithm. Fluid volumes and complete resolution was automatically assessed throughout the study. The impact of fluid location and volumes on best-corrected visual acuity was computed using mixed-effects regression models. RESULTS: Baseline fluid quantifications for 348 eyes from 348 patients were balanced (all P > 0.05). No quantitative differences in SRF/intraretinal fluid between the treatment arms was found at any study-specific time point (all P > 0.05). Compared with qualitative assessment, the proportion of eyes without SRF/intraretinal fluid did not differ between the groups at any time point (all P > 0.05). Intraretinal fluid in the central 1 mm and SRF in the 1-mm to 6-mm macular area were negatively associated with best-corrected visual acuity (-2.8 letters/100 nL intraretinal fluid, P = 0.007 and -0.20 letters/100 nL SRF, P = 0.005, respectively). CONCLUSION: Automated fluid quantification using artificial intelligence allows objective and precise assessment of macular fluid volume and location. Precise determination of fluid parameters will help improve therapeutic efficacy of treatment in neovascular age-related macular degeneration.

PURPOSE To evaluate the change in the fovea's postoperative location after successful pars plana vitrectomy with combined epiretinal and internal limiting membrane peeling in patients with idiopathic epiretinal membranes (iERMs). METHODS In this prospective study 32 eyes of 32 patients with iERMs were followed from baseline before until 3 months after surgery. Study measures included 4-m Early Treatment Diabetic Retinopathy Study best-corrected visual acuity, enhanced-depth imaging-optical coherence tomography, and intraoperative fundus photographs. Foveal movement was assessed by measuring the change in the papillofoveal distance (∆PFD). RESULTS Mean ∆PFD in the study eye was -124 µm (±138) and -272 µm (±213) one day and 3 months after surgery, respectively. Mean ∆PFD after 3 months was greater in the study than in the fellow eye (P < 0.001). ∆PFD at Month 3 did not correlate with the internal limiting membrane area peeled (P = 0.78). CONCLUSION Foveal movement starts immediately after surgery and causes a statistically significant reduction in PFD after uneventful macular pucker surgery. ∆PFD correlates statistically significantly with baseline best-corrected visual acuity and baseline central retinal thickness. The internal limiting membrane peeling size had no significant effect on the amount of postoperative foveal dislocation.

Purpose To explore the regional distribution of macular neovascularization type 3 (MNV3). Methods Seventy-eight eyes of 78 patients were reviewed. We defined the location of each lesion after applying a modified ETDRS grid and the incidence of simultaneous MNV1 or 2. Also, we investigated the distribution of MNV3 at the outline of the foveal avascular zone and when the diameter of foveal avascular zone was less than 325 µm. Results The distribution of MNV3 was 4 lesions (5%) from the center to 500 µm, 72 (92%) from 500 µm to 1500 µm, and 2 (3%) from 1,500 µm to 3000 µm. The distribution in respect of the ETDRS fields was 7 (9%) nasal, 16 (20%) superior, 32 (40%) temporal, and 23 (31%) inferior. No additional MNV1 or 2 were found elsewhere. Most lesions tended to distribute along straight bands radiating from the perifoveal area, mainly in the temporal half (72%). None of the cases had MNV3 at the boundary of the foveal avascular zone. Only five cases had foveal avascular zone diameter of less than 325 µm, the closest lesion was 425 µm away from the center. Conclusion MNV3 lesions are most likely neither symmetrical nor uniformly distributed. They have a higher affinity to distribute radially in the temporal perifoveal area.

Purpose To quantify morphologic photoreceptor integrity during anti-vascular endothelial growth factor (anti-VEGF) therapy of neovascular age-related macular degeneration and correlate these findings with disease morphology and function. Methods This presents a post hoc analysis on spectral-domain optical coherence tomography data of 185 patients, acquired at baseline, Month 3, and Month 12 in a multicenter, prospective trial. Loss of the ellipsoid zone (EZ) was manually quantified in all optical coherence tomography volumes. Intraretinal cystoid fluid, subretinal fluid (SRF), and pigment epithelial detachments were automatically segmented in the full volumes using validated deep learning methods. Spatiotemporal correlation of fluid markers with EZ integrity as well as bivariate analysis between EZ integrity and best-corrected visual acuity was performed. Results At baseline, EZ integrity was predominantly impaired in the fovea, showing progressive recovery during anti-vascular endothelial growth factor therapy. Topographic analysis at baseline revealed EZ integrity to be more likely intact in areas with SRF and vice versa. Moreover, we observed a correlation between EZ integrity and resolution of SRF. Foveal EZ integrity correlated with best-corrected visual acuity at all timepoints. Conclusion Improvement of EZ integrity during anti-VEGF therapy of neovascular age-related macular degeneration occurred predominantly in the fovea. Photoreceptor integrity correlated with best-corrected visual acuity. Ellipsoid zone integrity was preserved in areas of SRF and showed deterioration upon SRF resolution.

PURPOSE The impact of peripheral retinal lesions (PL) visualized with ultra-wide-field imaging on diabetic retinopathy (DR) remains unclear. The purpose of this study was to assess the presence of PL and their association with macular microvasculopathy, metabolic dysfunction, and neurodegeneration in patients with Type II diabetes and early retinal disease. METHODS Forty-five degree color fundus (Topcon) and 200° ultra-wide-field images (Optos) were assessed for the presence and severity of DR. Lesions anterior to the 45° were considered peripheral. The foveal avascular zone area, perimeter and acircularity index, and foveal full-retina and parafoveal superficial/deep complex vessel density were evaluated with RTVue optical coherence tomography angiography. Vessel oxygen saturation was measured with oximetry. Peripapillary retinal nerve fiber and individual macular retinal layer thicknesses were measured with Spectralis optical coherence tomography. RESULTS Among the 161 eyes (80 left eyes) of 81 patients (34 female), 64 (39.8%) showed higher levels of DR on ultra-wide-field than on 45° fundus images (P < 0.0001). PL were identified in 97 eyes (60.3%) and in 59 among 115 eyes without central signs of DR. No significant correlation to biomarkers of central microvascular disease (foveal avascular zone/vessel density variables), oxygen saturation, and retinal layer thickness was found. CONCLUSION Ultra-wide-field imaging helps to detect more eyes with early DR due to the detection of PL, which appear independently of biomarkers of macular microvascular impairment, metabolic function, and neuropathy in eyes without central signs of DR. These results suggest that the evaluation of the retinal periphery may become crucial in DR screening if PL are proven to influence disease outcomes.

Purpose To compare area measurements between swept source optical coherence tomography angiography (SSOCTA), fluorescein angiography (FA), and indocyanine green angiography (ICGA) after applying a novel deep-learning-assisted algorithm for accurate image registration. Methods We applied an algorithm for the segmentation of blood vessels in FA, ICGA, and SSOCTA images of 24 eyes with treatment-naive neovascular age-related macular degeneration. We trained a model based on U-Net and Mask R-CNN for each imaging modality using vessel annotations and junctions to estimate scaling, translation, and rotation. For fine-tuning of the registration, vessels and the elastix framework were used. Area, perimeter, and circularity measurements were performed manually using ImageJ. Results Choroidal neovascularization lesion size, perimeter, and circularity delineations showed no significant difference between SSOCTA and ICGA (all P > 0.05). Choroidal neovascularization area showed excellent correlation between SSOCTA and ICGA (r = 0.992) and a Bland-Altman bias of -0.10 ± 0.24 mm. There was no significant difference in foveal avascular zone size between SSOCTA and FA (P = 0.96) and an extremely small bias of 0.0004 ± 0.04 mm and excellent correlation (r = 0.933). Foveal avascular zone perimeter was not significantly different, but foveal avascular zone circularity was significantly different (P = 0.047), indicating that some small cavities or gaps may be missed leading to higher circularity values representing a more round-shaped foveal avascular zone in FA. Conclusion We found no statistically significant differences between SSOCTA and FA and ICGA area measurements in patients with treatment-naive neovascular age-related macular degeneration after applying a deep-learning-assisted approach for image registration. These findings encourage a paradigm shift to using SSOCTA as a first-line diagnostic tool in neovascular age-related macular degeneration.

Purpose To characterize retinal morphology differences among different types of choroidal neovascularization and visual function changes at the onset of exudative age-related macular degeneration. Methods In a post hoc analysis of a prospective clinical study, 1,097 fellow eyes from subjects with choroidal neovascularization in the study eye enrolled in the HARBOR trial were evaluated. The onset of exudation was diagnosed on monthly optical coherence tomography by two masked graders. At conversion as well as 1 month earlier, pigment epithelial detachment, intraretinal cystoid fluid, subretinal fluid, subretinal hyperreflective material, as well as ellipsoid zone and external limiting membrane loss were quantitatively analyzed. Hyperreflective foci, retinal pigment epithelial defects, haze and vitreoretinal interface status were evaluated qualitatively. Main outcome measures included visual acuity and rates of morphologic features at conversion and 1 month earlier. Results New-onset exudation was detected in 92 eyes. One month before conversion, hyperreflective foci, pigment epithelial detachment, retinal pigment epithelial defects, and haze were present in the majority of eyes. At the onset of exudation, the volumes of intraretinal cystoid fluid, subretinal fluid, subretinal hyperreflective material and pigment epithelial detachment, and the areas of external limiting membrane and ellipsoid zone loss significantly increased. The mean vision loss was -2.2 letters. Pathognomonic patterns of the different choroidal neovascularization types were already apparent 1 month before conversion. Conclusion Characteristic choroidal neovascularization-associated morphological changes are preceding disease conversion, while vision loss at the onset of exudation is minimal. Individual lesion types are related to specific changes in optical coherence tomography morphology already before the time of conversion. Our findings may help to elucidate the pathophysiology of neovascular age-related macular degeneration and support the diagnosis of imminent disease conversion.

PURPOSE To evaluate the effect of patients' clinical information on experts' diagnoses of retinopathy of prematurity (ROP) and decisions to treat. METHODS Seven experts assessed wide-field fundus photographs of eyes of 52 premature infants of ≤30 weeks' gestational age or ≤1,500 g birthweight (BW) for ROP diagnosis (stage, plus disease, and aggressive posterior ROP) and the necessity for treatment for 2 days. On Day 1, they were masked to all patient data. On Day 2, they were given information on gestational age and BW. RESULTS A significant shift in the experts' ratings toward a less aggressive ROP grading stage (P = 0.006) and less frequent decision for intervention (P = 0.021) was observed after receipt of patients' clinical information. This was truer for heavier/less premature infants (gestational age ≥ 28 0/7 weeks or BW ≥ 900 g) than those with very low BWs/high prematurity (gestational age < 24 0/7 weeks or BW < 600 g) (ROP stage P = 0.009 vs. P = 0.399, treatment decision P = 0.022 vs. P = 0.648). CONCLUSION These results suggest knowledge of patients' clinical information influences the grading of ROP disease and decision for treatment. Retinopathy of prematurity staging seemed to be set at a lower level and the decision for treatment at a higher threshold for heavier/less premature babies. Our findings may have implications for further refinements in ROP assessment.

PURPOSE Reduced thickness of the ganglion cell inner plexiform layer indicates diabetic neurodegeneration and can be assessed by spectral domain optical coherence tomography. The authors investigated the comparability of ganglion cell inner plexiform layer measurements from two spectral domain optical coherence tomography devices in patients with diabetic macular edema (DME). METHODS Analysis of optical coherence tomography data sets of eyes with and fellow eyes without DME. Macular cube scans of sufficient signal strength on Cirrus (Carl Zeiss Meditec) were compared with correlating scans on Spectralis (Heidelberg Engineering, Germany) being acquired within 1 hour. RESULTS Eighty-one equivalent data sets for 20 eyes with DME (20 patients; 6 female) and 33 for 9 fellow eyes without DME (9 patients; 2 female) were included from each device. In DME eyes, mean ganglion cell inner plexiform layer thicknesses were 62.5 ± 20.4 μm on Cirrus and 91.2 ± 9.3 μm on Spectralis. Ganglion cell inner plexiform layer was significantly thicker on Spectralis analyzing eyes with and without signs of DME (P < 0.001). The ganglion cell inner plexiform layer variance (54.2%) related to device differences decreased to 34.8% in eyes without DME. CONCLUSION Ganglion cell inner plexiform layer data from different devices vary considerably and cannot be used interchangeably. As spectral domain optical coherence tomography is indispensable for identifying ganglion cell loss associated with diabetic neurodegeneration, clinicians should be aware of the difference when monitoring patients.

PURPOSE To evaluate retinal sensitivity in patients with diabetic macular edema who received intravitreal aflibercept injection (IAI) or laser. METHODS A substudy included 46 patients from DA VINCI (a randomized, double-masked Phase 2 study) receiving either laser, 0.5 mg IAI every 4 weeks, 2 mg IAI every 4 weeks, 2 mg IAI every 8 weeks after 3 monthly doses (2q8), or 2 mg IAI as-needed after 3 monthly doses for 52 weeks. Retinal sensitivity was measured in one (central), five (one central and four inner), and eight (four inner and four outer) optical coherence tomography subfields. RESULTS Mean best-corrected visual acuity improvement in the subgroup at Week 52 was 3.3 letters with laser and ranged from 5.4 to 16.3 letters in the IAI groups. Retinal sensitivity of laser patients at Week 52 was comparable with baseline in the central optical coherence tomography subfield but decreased in the five and eight optical coherence tomography subfields. Compared with laser, retinal sensitivity significantly increased with IAI in the 2q8 and pooled IAI groups in the 5 and 8 optical coherence tomography subfields at Week 52 (P < 0.05). CONCLUSION Intravitreal aflibercept injection improved best-corrected visual acuity and retinal sensitivity in this subgroup of patients. Laser may cause a deterioration of macular function that is not detectable with best-corrected visual acuity testing.

PURPOSE To evaluate changes in the distribution and morphology of intraretinal microexudates and hard exudates (HEs) during intravitreal anti-vascular endothelial growth factor therapy in patients with persistent diabetic macular edema. METHODS Twenty-four patients with persistent diabetic macular edema after photocoagulation were investigated in this prospective cohort study. Each eye was assigned to a loading dose of three anti-vascular endothelial growth factor treatments at monthly intervals. Additional single treatments were performed if diabetic macular edema persisted or recurred. Intraretinal exudates were analyzed over 6 months using spectral domain optical coherence tomography (SD-OCT) and fundus photography. RESULTS Before treatment, microexudates were detected by SD-OCT as hyperreflective foci in 24 eyes, whereas HEs were seen in 22 eyes. During therapy, HE increased significantly in number and size. This was accompanied by accumulation of microexudates in the outer retina. Enlargement of hyperreflective structures in SD-OCT was accompanied by enlargement of HE at corresponding fundus locations. A rapid reduction in diabetic macular edema was seen in all patients, but to varying degrees. Patients with hemoglobin A1c levels

To investigate pigmentation characteristics of the retinal pigment epithelium (RPE) in patients with albinism using wide-field polarization-sensitive optical coherence tomography compared with intensity-based spectral domain optical coherence tomography and fundus autofluorescence imaging.Five patients (10 eyes) with previously genetically diagnosed albinism and 5 healthy control subjects (10 eyes) were imaged by a wide-field polarization-sensitive optical coherence tomography system (scan angle: 40 × 40° on the retina), sensitive to melanin contained in the RPE, based on the polarization state of backscattered light. Conventional intensity-based spectral domain optical coherence tomography and fundus autofluorescence examinations were performed. Retinal pigment epithelium-pigmentation was analyzed qualitatively and quantitatively based on depolarization assessed by polarization-sensitive optical coherence tomography.This study revealed strong evidence of polarization-sensitive optical coherence tomography to specifically image melanin in the RPE. Depolarization of light backscattered by the RPE in patients with albinism was reduced compared with normal subjects. Heterogeneous RPE-specific depolarization characteristics were observed in patients with albinism. Reduction of depolarization observed in the light backscattered by the RPE in patients with albinism corresponds to expected decrease of RPE pigmentation. The degree of depigmentation of the RPE is possibly associated with visual acuity. Findings suggest that different albinism genotypes result in heterogeneous levels of RPE pigmentation.Polarization-sensitive optical coherence tomography showed a heterogeneous appearance of RPE pigmentation in patients with albinism depending on different genotypes.

PURPOSE To identify the morphologic changes secondary to macular grid photocoagulation in diabetic macular edema in vivo using spectral domain optical coherence tomography. METHODS In this prospective cohort study, 13 consecutive patients with vision loss because of clinically significant macular edema associated with diabetes mellitus Type 2 underwent grid laser treatment (PASCAL). Best-corrected visual acuity, Spectralis optical coherence tomography, infrared fundus imaging, and biomicroscopy were performed at baseline, Day 1, Week 1, and Months 1, 2, and 3 after treatment. Fluorescein angiography was performed at baseline and at 3 months. RESULTS Mean central 1-mm thickness decreased significantly from 438 ± 123 μm (mean ± SD) at baseline to 391 ± 111 μm (P < 0.05) at 3 months with a nonsignificant trend of best-corrected visual acuity improvement. A wipeout of the photoreceptor layer and the inner segment/outer segment line together with an alteration of the overlaying outer nuclear layer and external limiting membrane was seen at Day 1. The lesion was reduced to a focal hyperreflective deposit on the retinal pigment epithelium boundary. In 55% of lesions, the external limiting membrane as well as the previously interrupted inner segment/outer segment line revealed intact continuity at Month 3. In some areas, repair was incomplete indicated by a focal condensation interrupting the inner segment/outer segment line in the lesion center. CONCLUSION In vivo imaging of morphologic lesion repair in human eyes after PASCAL grid laser of diabetic macular edema demonstrates progressive restoration of the external limiting membrane and inner segment/outer segment integrity as previously described in animal models.

Purpose: To identify and quantify angiogenic and inflammatory cytokines in aqueous and vitreous humor in eyes with untreated uveal melanoma and to analyze clinicopathologic correlations. Methods: Intraocular fluid samples of patients (uveal melanoma aqueous n = 21, vitreous n = 34) and controls (cataract aqueous n = 41, vitreomacular traction aqueous n = 35, vitreous n = 36) were taken intraoperatively and analyzed using Luminex xMAP suspension array technology. Beadlyte kits were used for detection of 28 different cytokines. Results: Flt-3 ligand, interleukin (IL) 1α, IL-6, IL-8, interferon-γ inducible protein (IP)-10, monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1α, platelet-derived growth factor AA, and vascular endothelial growth factor were significantly elevated in aqueous and vitreous of melanoma eyes when compared with controls. Eotaxin was significantly elevated in aqueous, and IL-7 and RANTES were significantly elevated in vitreous samples of melanoma eyes. Interferon-γ inducible protein 10, macrophage inflammatory protein 1α (aqueous and vitreous), Flt-3 ligand, IL-6, IL-8, and MCP-1 (vitreous) correlated with tumor dimensions. Further correlations were found between infiltration of Bruch membrane and Flt-3 ligand, MCP-1 (aqueous and vitreous), IL-8, interferon-γ inducible protein 10, macrophage inflammatory protein 1α, and platelet-derived growth factor AA (vitreous). Analyzing 16 paired aqueous and vitreous melanoma samples, Flt-3 ligand, IL-7, interferon-γ inducible protein 10, MCP-1, and platelet-derived growth factor AA were significantly elevated in vitreous, and IL-1α and vascular endothelial growth factor in aqueous samples. Conclusion: A range of significantly elevated angiogenic, inflammatory, and chemotactic cytokines in eyes with uveal melanoma supports the link between inflammation and tumorigenesis.

Purpose To evaluate the 3-year therapeutic benefit of intravitreal bevacizumab in neovascular related macular degeneration (nAMD) in a standard clinical setting involving 3 initial injections and a pro re nata regimen as recommended in the PRONTO study. Methods In this interventional clinical study, 181 eyes of 160 consecutive patients with active neovascular related macular degeneration meeting recommended criteria for inclusion and protocol criteria for anti-vascular endothelial growth factor therapy undergoing intravitreal bevacizumab monotherapy were observed. Data of treatment-naive eyes (Group 1, n = 114) were analyzed separately from eyes that had undergone previous photodynamic therapy plus intravitreal triamcinolone (Group 2, n = 67). Re-treatment criteria were based on clinical outcome following the official European label regimen. After 1 year of continuous service at an academic referral center, follow-up was performed in private practices in collaboration with the referral center. Main outcome parameters were best-corrected visual acuity and central retinal thickness. Results After 3 years, best-corrected visual acuity decreased in the overall population (0.23 ± 0.16 to 0.16 ± 0.21. P = 0.002) and in both groups compared with baseline (0.24 ± 0.21 to 0.17 ± 0.21, Group 1, P = 0.03; 0.22 ± 0.19 to 0.16 ± 0.21, Group 2, P > 0.05), whereas central retinal thickness increased in the overall population (291 ± 92 to 319 ± 110 μm, P = 0.01) and in both groups (291 ± 96 to 325 ± 117 μm, Group 1, P > 0.05; 290 ± 83 to 308 ± 96 μm, Group 2, P > 0.05) because of chronic cystic degeneration changes of the macula. Mean treatment rate was 5.1 ± 3.9 (Group 1) versus 3.7 ± 2.7 (Group 2, P = 0.01). Five cases of severe intraocular inflammation after intravitreal bevacizumab were documented. Discussion While the functional and morphological benefits persisted for the first year after intravitreal bevacizumab treatment, after this time both functional and morphologic results were disappointing during long-term follow-up with visual acuity loss as the main retreatment criterion. After stabilization of the disease, a monthly follow-up of optical coherence tomography and re-treatment based on morphologic, clinical, and vision outcomes may increase the efficacy in patients with neovascular related macular degeneration under anti-vascular endothelial growth factor treatment.

PURPOSE Idiopathic juxtafoveal telangiectasia (IJT) is characteristically associated with pigmentary changes. Polarization-sensitive spectral-domain optical coherence tomography (PS-SD-OCT) enables imaging of the retinal pigment epithelium (RPE) and similar melanin-containing structures based on specific polarization properties. This study examined IJT with the latest-generation SD-OCT and PS-SD-OCT, identifying pathophysiologically relevant characteristics of the retinal layers and RPE. METHODS Twenty-two eyes of 12 patients with IJT were examined by PS-SD-OCT, with special focus on RPE detection and segmentation. Furthermore, SD-OCT technology (Cirrus, Spectralis, and 3D-OCT-1000) was applied. Characteristics of the retinal layers and RPE were evaluated. A classification system based on OCT characteristics of IJT was suggested. RESULTS Polarization-sensitive spectral-domain optical coherence tomography together with SD-OCT identified characteristic patterns of IJT, used to classify eyes into three distinct groups. Group 1 (5 eyes) revealed discrete alterations in the inner retinal layers; group 2 (12 eyes) showed irregularities of the junction between the inner and outer photoreceptor segments with outer retinal atrophy but an intact RPE. Group 3 (5 eyes) revealed RPE irregularities and loss in addition to intraretinal alterations and photoreceptor abnormalities. CONCLUSION This study described characteristic morphologic changes in IJT based on PS-SD-OCT and SD-OCT. Morphologic changes were classified, possibly leading to an OCT-based grading scheme. The intensity images of SD-OCT verified intraretinal and photoreceptor irregularities in great detail, whereas PS-SD-OCT additionally showed RPE alterations.

The purpose of this study was to determine the concentrations of angiogenic and inflammatory markers in human eyes with diffuse diabetic macular edema before and during therapy with intravitreal bevacizumab and their association with disease activity.In a prospective clinical trial, 10 eyes of 10 consecutive patients with vision loss because of diabetic macular edema were compared with 10 eyes of 10 age-matched controls. Bevacizumab was administered at baseline; retreatments were given monthly according to disease activity. During a follow-up of 6 months, aqueous humor samples were taken each time intravitreal therapy was administered. A multiplex assay was used for measurement of 12 different growth factors and cytokines.Aqueous humor of eyes with diabetic macular edema demonstrated a significantly increased expression of monocyte chemoattractant protein-1 and interleukin-8 and higher, but not significant, levels of interleukin-6 and vascular endothelial growth factor. Intravitreal therapy with bevacizumab resulted in a significant decrease of vascular endothelial growth factor below physiologic levels. This change was not associated with clinical disease activity as measured by visual acuity and central retinal thickness.Eyes with diabetic macular edema showed a different profile of monocyte chemoattractant protein-1 and interleukin-8 as compared with controls. The intraocular vascular endothelial growth factor expression decreased significantly after the first intravitreal injection of bevacizumab; this reduction was prolonged by consecutive monthly retreatment.

To compare different spectral domain optical coherence tomography devices regarding retinal thickness values in patients with diabetic macular edema and to correlate the results with conventional time domain Stratus OCT data.Thirty eyes of 30 consecutive patients with diabetic macular edema were included into a prospective study. The macula was examined by Spectralis HRA+OCT, Cirrus HD-OCT, 3D OCT-1000, and Stratus OCT. The procedures' sequence was performed by a single experienced technician in a randomized fashion according to a computer-generated list. In each eye, foveal thickness, foveal volume, and total macular volume were measured automatically. Intraclass correlation, coefficients of variance, and coefficients of repeatability were calculated.Foveal thickness differed between the particular devices with a mean ± SD ranging from 359.97 ± 105.84 μm to 437.70 ± 115.84 μm. Correlation between the different OCT devices resulted in r0.7 (Pearson), and intraclass correlation was0.9. Agreement of measurements was assessed showing a mean difference of foveal thickness values ranging from 19.2 μm to 77.7 μm (P0.05) and coefficients of repeatability ranging from 37.7 μm to 87.4 μm.While intradevice reproducibility is satisfactory, retinal thickness and volume measurements should not be used interchangeably because measurements differed significantly between systems. The lack of interdevice agreement seems to be related to the different segmentation algorithm of thickness measurement and should be considered because it may strongly influence treatment decisions and conclusions.

OBJECTIVE: To evaluate changes in central retinal sensitivity in patients with neovascular age-related macular degeneration after systemic bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) therapy. METHODS: For all eyes, the central 12 x 12 degrees visual field was recorded using the MP 1 Microperimeter (Nidek, Gamagori, Japan) at baseline and 1 week, 1 month, 3 months, and 6 months after initial treatment. Patients received systemic anti-vascular endothelial growth factor (VEGF) therapy with three initial bevacizumab infusions at 2-week intervals. Retreatment during follow-up was performed only in cases of choroidal neovascularization recurrence. Seven patients (12 eyes) received bevacizumab infusions at a dose of 5 mg/kg, and 7 patients (9 eyes), at a dose of 2.5 mg/kg. RESULTS: Of 41 stimulation points, a mean absolute scotoma of 15 missed stimulation points was measured at baseline, which decreased to 10 missed stimulation points at month 3 (-5; P = 0.005) and to 11 stimulation points at month 6 (-4; P = 0.106). The mean absolute scotoma size (in % of total tested area) decreased from 33% to 22% (-11%; P = 0.011) at month 3 and to 23% (-10%, P = 0.123) at month 6. Mean differential light threshold increased significantly throughout the observation period from 3.8 dB at baseline to 5.5 dB (+1.7 dB; P = 0.012) at month 6. CONCLUSIONS: Systemic bevacizumab therapy induced a significant increase in mean retinal sensitivity at month 6 of follow-up and a significant decrease of mean absolute scotoma size at month 3. The MP 1 Microperimeter proved to be a valuable tool in the evaluation of functional benefits and retinal safety of anti-VEGF therapy with systemic bevacizumab.

To document the long-term follow-up of patients with circumscribed choroidal hemangioma who were treated with verteporfin photodynamic therapy (PDT).Fifteen patients were included in a prospective interventional case series. Verteporfin PDT as a bolus infusion of 6 mg/m body surface area and a light dose of 100 J/cm at 689 nm applied over 166 seconds were administered. Standardized evaluation was performed every 3 months within the first year and at 12-month intervals during follow-up.At baseline, all patients presented with significant vision loss ranging from 20/26 to 20/500. During a mean follow-up of 36.6 months (range, 12-66 months), no patient had evidence of recurrence. Mean final visual acuity ranged from 20/20 to 20/400. In all patients, complete and permanent regression with no signs of tumor regrowth or recurring subretinal fluid was found. Of 15 patients, 13 had a substantial increase in visual acuity (range, 2-9 lines), and 2 patients' visual acuity remained stable. Chorioretinal atrophy at the previous tumor site did not enlarge over time. Retreatments after completion of the primary treatment were not necessary.Persistent and complete absence of choroidal hemangioma associated with persistent improvement in visual acuity and central visual fields can be obtained with verteporfin PDT.

OBJECTIVE: The authors report the clinical findings of a civilian patient who unintentionally looked into the laser beam of a military range finder. Detailed information on the range finder is given. The objective is to illustrate the potential danger of such devices and to give detailed information on the device, the clinical findings associated with exposure, and the laser-tissue interaction mechanism. METHODS: The patient was examined with fluorescein angiography, indocyanine green angiography, microperimetry, and optical coherence tomography, both in the acute stage (2 hours) and 4 weeks later. Fluorescein angiography was performed again 4 months later. A total of 100 mg prednisone tapered over 9 days was prescribed. Additionally, 50 microg tissue plasminogen activator (TPA) and 0.5 mL pure C2F6 were injected in the vitreous. RESULTS: In the acute phase, hemorrhage was located beneath the retina, primarily beneath the retinal pigment epithelium. Retinal defects as seen initially over the subretinal blood were reduced after 4 weeks, but a retinal defect ranging from the lasered site toward the fovea remained. Visual acuity slightly increased from 20/100 to 20/63 after 4 weeks. Indocyanine green angiography showed a large hypofluorescent spot in the macula. Four months after the accident, a classic choroidal neovascularization developed, originating from the lasered site. The technical parameters of the range finder were: Nd:YAG laser (1,064 nm), pulse duration 10 ns, beam divergence 1.5 mrad, energy 10 mJ. CONCLUSION: A range finder can produce severe macular injury. The primary laser-tissue interaction mechanism seems to be explosive disruption of choroidal tissue. Intravitreal injection of TPA and C2F6 did not show a clear benefit to such laser lesions. A late complication can be secondary choroidal neovascularization. Language: en