Detailed analysis of retinal morphology in patients with diabetic macular edema (DME) randomized to ranibizumab or triamcinolone treatment.

PURPOSE: Our purpose was to compare the impact in diabetic macula edema (DME) of two intravitreal drugs (0.5 mg ranibizumab vs. 8 mg triamcinolone) on changes in retinal morphology in spectral-domain optical coherence tomography (SD OCT) images, color fundus photography (CF) and fluorescein angiography (FA) images during a 1-year follow-up. METHODS: Post hoc analysis was conducted of morphologic characteristics in OCT, FA and CF images of eyes with a center involving DME that were included in a prospective double-masked randomized trial. Eligible patients were divided at random into two groups receiving either pro re nata treatment with 0.5 mg ranibizumab or 8 mg triamcinolone after a fixed loading dose. OCT and CF images were acquired at monthly visits and FA images every three months. RESULTS: Twenty-five eyes of 25 patients (ranibizumab: n = 10; triamcinolone: n = 15) were included in this study. Patients treated with ranibizumab showed better visual acuity results after 12 months than patients receiving triamcinolone (p = 0.015) although edema reduction was similar (p = 0.426) in both groups. The initial effect on macular edema shedding after a single ranibizumab injection could be amplified with the following two injections of the loading dose. After a single injection of triamcinolone the beneficial initial effect on the macula edema faded within 3 months. Subretinal fluid and INL cystoid spaces diminished early in the course of treatment while fluid accumulation in the ONL seemed to be more persistent in both treatment arms. In FA, the area of leakage diminished significantly in both treatment arms. After repeated injections the morphologic OCT and FA characteristics of the treatment arms converged. CONCLUSIONS: Despite the higher dosage of triamcinolone, both therapies were safe and effective for treating diabetic macular edema. Fluid accumulation in the INL and subretinal space was more responsive to therapy than fluid accumulation in the ONL. Clinicaltrials.gov : NCT00682539.

COMPARISON OF GANGLION CELL INNER PLEXIFORM LAYER THICKNESS BY CIRRUS AND SPECTRALIS OPTICAL COHERENCE TOMOGRAPHY IN DIABETIC MACULAR EDEMA.

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.

RETINAL MORPHOMETRY CHANGES MEASURED WITH SPECTRAL DOMAIN-OPTICAL COHERENCE TOMOGRAPHY AFTER PAN-RETINAL PHOTOCOAGULATION IN PATIENTS WITH PROLIFERATIVE DIABETIC RETINOPATHY.

PURPOSE: To identify the effects of pan-retinal laser treatment on the integrity of neurosensory retinal layers. METHODS: Patients were examined with fluorescence angiography after a standardized examination for diabetic retinopathy and a peripapillary ring scan with spectral domain optical coherence tomography. A single-session pan-retinal photocoagulation was performed using the PASCAL pattern scanning argon laser applying a minimum of 1,500 spots. Optical coherence tomography was evaluated more than 6 months. RESULTS: Eighteen eyes of 12 consecutive patients with new onset, treatment-naive proliferative diabetic retinopathy secondary to diabetes Type 2 were treated and retinal optical coherence tomography morphology evaluated. Retinal nerve fiber layer thickness increased statistically significantly from baseline to week 1, when it reached its peak. The combined thickness of the outer plexiform and the inner nuclear layers and the combined thickness of the inner plexiform and the ganglion cell layers showed no relevant changes. The combined thickness of the retinal pigment epithelium and the photoreceptor cell layers decreased at month 1 followed by a steady increase in thickness, which remained below baseline values over time. CONCLUSION: Pan-retinal photocoagulation in proliferative diabetic retinopathy leads to a slowly reversible, marked biological response with statistically significant morphometric changes detected by spectral domain optical coherence tomography. Swelling of the retinal nerve fiber and outer nuclear layers induce an increase in peripapillary total retinal thickness. Simultaneously, the photoreceptor and retinal pigment epithelium layers decrease in thickness. These changes indicate diffuse retinal inflammation after pan-retinal laser therapy.

IOL decentration sensitivity according to spatial frequencies.

BACKGROUND/AIMS: Investigation of the decentration sensitivity of monofocal intraocular implants with a focus on different aberration corrections depending on different spatial frequencies. METHODS: Using an optical bench, the decentration sensitivities of an intraocular lens (IOL) with a high spherical aberration correction of -0.27 µm (ZCB00 Johnson & Johnson), an IOL with an aberration correction of -0.20 µm (Primus HD OphthalmoPro) and an IOL with an aberration neutral design (CT Asphina 409MP Carl Zeiss Meditec) were evaluated for Strehl ratio values and for 25, 50 and 100 lp/mm. Two different corneas with +0.13 µm and +0.28 µm were used. The lenses were tested in the best centration and up to a decentration of 0.5 mm. RESULTS: Decentration sensitivity affects high spatial frequencies more than lower ones. The possible decentration sensitivity is determined by the amount of spherical aberration of the cornea. The effective decentration sensitivity is determined by the extent to which these spherical aberrations are compensated. If these are not compensated, there is hardly any decentration sensitivity. CONCLUSION: High spatial frequencies are more affected by decentration sensitivity. The decentration sensitivity of an IOL is determined by the extent to which the spherical aberration of the cornea is corrected.

Retinal architecture recovery after grid photocoagulation in diabetic macular edema observed in vivo by spectral domain optical coherence tomography.

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.

Through-Focus Response of Extended Depth of Focus Intraocular Lenses.

PURPOSE: To investigate extended depth of focus intraocular lenses (EDOF IOLs), intended to extend the depth of field after cataract surgery in a comparative study at the optical bench. METHODS: An optical bench with either green or white light was used for this study. The artificial cornea used exhibited a spherical aberration of 0.2 µm. Examinations of the following lenses with a pupil opening of 3 and 4.5 mm were carried out: AcrySof IQ Vivity (Alcon Laboratories, Inc), Isopure (PhysIOL), Tecnis Eyhance (Johnson & Johnson), Vivinex Impress (Hoya Surgical Optics), and xact (Santen). RESULTS: Using green light and a pupil aperture of 3 mm, the AcrySof IQ Vivity showed the highest light energy for the intermediate area, whereas the Isopure and Vivinex Impress provided the highest energy for distance vision. Under the same examination conditions with a pupil opening of 4.5 mm, all lenses showed a low light distribution for the intermediate range. Regarding light distribution for distance, the Tecnis Eyhance had the highest light intensity. Using white light, the curves became much wider and more similar to each other. CONCLUSIONS: The five EDOF lenses investigated differ mainly by their different weighting of energy between the far and intermediate ranges. [J Refract Surg. 2022;38(8):497-501.].

Longitudinal analysis of microvascular perfusion and neurodegenerative changes in early type 2 diabetic retinal disease.

AIM: To prospectively monitor subclinical changes in capillary perfusion and retinal layer thickness in patients with type 2 diabetes and early diabetic retinal disease over 2 years. METHODS: In this longitudinal study we performed biannual retinal vascular imaging using optical coherence tomography angiography (RTVue) to analyse the foveal avascular zone (FAZ) area, perimeter, acircularity index (AI) and parafoveal superficial/deep vessel density (VD). Spectral-domain optical coherence tomography (Spectralis) was used to measure the thickness of nine macular layers and the peripapillary nerve fibre layer. RESULTS: Among 117 eyes (58 left) of 59 patients (21 female), 105 had no diabetic retinopathy (DR), 6 mild and 6 moderate non-proliferative DR at baseline. We found DR progression in 13 eyes at year 2. The FAZ area (+0.008±0.002 mm2/year, p<0.0001), perimeter (+0.036±0.010 mm/year, p=0.006) and AI (+0.005±0.002/year, p=0.0280) increased significantly. A pronounced decrease was found in the superficial (-1.425±0.290%/year, p<0.0001) but not the deep VD. Inner neuroretinal loss was confined to the ganglion cell (-0.539±0.150 µm/year, p=0.0004) and the inner plexiform layer (-0.361±0.127 µm/year, p=0.0045). In the outer retina, we observed a statistically significant decrease in thickness in the outer plexiform, photoreceptor layer and pigment epithelium of -0.921±0.161 µm/year, -0.325±0.139 µm/year and -0.385±0.084 µm/year, respectively. CONCLUSION: Subclinical signs of microangiopathy and neurodegeneration appear in parallel and are highly progressive even in the earliest stages of diabetic retinal disease. Trial registration number EudraCT20156000239634.

Comparison of safety and effectiveness between 23-gauge and 25-gauge vitrectomy surgery in common vitreoretinal diseases.

PURPOSE: To assess and compare safety and effectiveness between 23-gauge and 25-gauge vitrectomy systems for the treatment of common vitreoretinal diseases in non-vitrectomized eyes. METHODS: Retrospective evaluation of patients who underwent pars plana vitrectomy from April 2018 to December 2019 at the Department of Ophthalmology and Optometry at the Medical University of Vienna (MUV) for the following indications: macular epiretinal membrane, macular hole, macular lamellar hole, vitreous hemorrhage, vitreous opacities, vitreomacular traction syndrome and macular edema. RESULTS: 201 eyes of 195 patients that underwent 23-gauge (n = 105 eyes) or 25-gauge (n = 96 eyes) vitrectomy were included in this study. The mean best-corrected visual acuity (BCVA) improved at 1-3 months postoperatively and beyond 3 months in both gauge groups. Risk of any complication within 1 month postoperatively was lower in the 25-gauge group, but the difference was statistically not significant (HR [95% CI]: 0.95 [0.53; 1.70], p = 0.85). Intraocular pressure less than 5 mmHg was observed in 2 eyes (2%) in the 23-gauge group at the first postoperative day. Intraocular pressure elevation over 25 mmHg occurred in 5 eyes (2 eyes, 2%, in 23-gauge and 3 eyes, 3%, in 25-gauge group) at postoperative day 1, between 7 and 28 days in 5 cases (2 eyes, 2%, in 23-gauge and 3 eyes, 3%, in 25-gauge group), and in 2 eyes (2%) of the 23-gauge group at postoperative day 145 and 61, respectively. Retinal detachment occurred in 1 eye (1%) in the 23-gauge and in 3 eyes (3%) in the 25-gauge group. We did not observe any cases of endophthalmitis. CONCLUSION: Results in terms of safety, surgical success and visual outcomes for the treatment of common vitreoretinal surgery indications seem to be comparable between 23-gauge and 25-gauge vitrectomy systems, indicating that the two gauge systems can be used equally in the clinical routine.

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.

Effect of retinal photocoagulation on intraretinal lipid exudates in diabetic macular edema documented by optical coherence tomography.

PURPOSE: To study the changes in the distribution and morphologic features of intraretinal microexudates after macular photocoagulation. DESIGN: Prospective cohort study. PARTICIPANTS: Thirteen treatment-naïve patients with clinically significant macular edema in type 2 diabetes. METHODS: Patients were treated with focal macular photocoagulation. Changes in the localization of hyperreflective foci were analyzed by spectral domain (SD) optical coherence tomography (OCT) during follow-up at day 1, week 1, and months 1, 2, 3, and 4 in defined areas. Further, fundus photography and infrared imaging were performed at all visits and findings were correlated to OCT results. MAIN OUTCOME MEASURES: Changes in retinal morphologic features detected in OCT. RESULTS: A dynamic change in the distribution pattern of hyperreflective foci was observed over 4 months after the photocoagulation. With the decrease of retinal thickness, the dots either resolved completely or became confluent at the apical border of the outer nuclear layer, and finally formed ophthalmoscopically detectable hard exudates during extended follow-up. In the event of retinal thickening despite laser treatment, the hyperreflective dots maintained their previous distribution throughout all retinal layers. As a fourth response, dissemination of plaques of hard exudates into multiple, separate, hyperreflective foci were detected. CONCLUSIONS: Hyperreflective foci in the retina seem to represent precursors or components of hard exudates. Their specific localization depends greatly on the presence of microvascular extravasation and intraretinal fluid accumulation. Retinal photocoagulation has a major impact on retinal edema and subsequently on the distribution of intraretinal lipid deposits. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

In vivo retinal morphology after grid laser treatment in diabetic macular edema.

PURPOSE: To analyze immediate in vivo intraretinal morphologic changes secondary to standardized grid photocoagulation using spectral domain optical coherence tomography (SD OCT). DESIGN: Prospective clinical trial. PARTICIPANTS: Thirteen consecutive patients with treatment-naïve clinically significant diabetic macular edema (DME). METHODS: Before and 1 day after standardized grid photocoagulation using the PASCAL system (Pattern Scan Laser, OptiMedica Corporation, Santa Clara, CA), Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) examinations based on an eye-tracking system, infrared fundus imaging, color fundus photography, and biomicroscopy were performed. A standardized visual acuity assessment (Early Treatment Diabetic Retinopathy Study protocol) and fluorescein angiography were performed at baseline. MAIN OUTCOME MEASURES: Morphologic changes secondary to grid laser treatment. RESULTS: One day after laser therapy, immediate morphologic alterations of only the outer retinal layers, that is, the retinal pigment epithelium (RPE), the photoreceptor layer (PRL), and the outer nuclear layer (ONL), were observed. The shape of the laser-induced lesions did not show a sagittal alteration pattern throughout all 3 of the layers, however, but rather seemed to follow an oblique pathway throughout the ONL, changing direction at the level of the external limiting membrane and proceeding sagittally through the PRL and RPE. These morphologic changes also induced biometric changes, such as a decrease in central retinal thickness combined with local thickening at the lesion site, especially in the PRL. CONCLUSIONS: Spectral domain optical coherence tomography provides new insight into the immediate morphologic changes after laser treatment using the PASCAL laser system. Standardized grid photocoagulation induces characteristic homogenous alteration in the neurosensoric retinal layers. Biometric changes, indicating an immediate effect, were observed within 1 day after treatment.

Posterior optic buttonholing prevents intraocular pressure peaks after cataract surgery with primary posterior capsulorhexis.

BACKGROUND: The performance of a primary posterior capsulorhexis (PPC) with and without posterior optic buttonholing (POBH) may significantly influence the intraocular pressure (IOP) after cataract surgery in age-related cataract patients. METHODS: The prospective randomized clinical study was performed at the department of Ophthalmology, Medical University of Vienna, Austria. Thirty consecutive cataract patients with bilateral same-day cataract surgery (60 eyes) under topical anesthesia were enrolled. In randomized order, cataract surgery with combined PPC/POBH was performed in one eye; in the other eye, cataract surgery was performed with PPC and in-the-bag implantation of the intraocular lens (IOL). Standardized IOP measurements by Goldmann applanation tonometry were performed preoperatively, 1, 2, 4, 6, 8 and 24 hours postoperatively, as well as 1 week and 1 month postoperatively. RESULTS: During the first 24 hours after surgery, all IOP measurements were significantly lower in eyes with combined PPC/POBH when compared to eyes with solitary PPC (p < 0.001). No IOP peaks of more than 27 mmHg were observed with combined PPC/POBH. In contrast, in eyes with PPC and in-the-bag IOL implantation, seven patients had an IOP peak of more than 27 mmHg and four IOP peaks of more than 30 mmHg. One week and 1 month postoperatively, IOP measurements were statistically comparable, and no significant differences could be observed between the two groups (p > 0.05). CONCLUSION: Postoperative IOP peaks after cataract surgery with sole PPC can be effectively prevented by the buttonholing of the IOL through the posterior capsulorhexis.

Association of macular perfusion status with microvascular parameters up to the far periphery in diabetic retinopathy using multimodal imaging.

BACKGROUND: The aim of our study was to investigate a possible association between macular perfusion status and retinal ischemia and leakage up to far peripheral retinal areas in eyes with early to advanced stages of diabetic retinopathy (DR). METHODS: In a retrospective, cross sectional analysis ultrawide field (UWF) color fundus photos (Optos, Optomap California) were graded for DR severity. Foveal avascular zone (FAZ) and vessel density from the superficial (SCP) and deep capillary plexus (DCP) were assessed on optical coherence tomography angiography (OCTA) scans (Topcon, DRI-OCT Triton). UWF angiography images were used to quantify leakage/ischemic index and number of microaneurysms (MA). Age, gender, disease duration, type of diabetes, HbA1C, hypertension, complications of diabetes and ocular history were recorded. Univariate mixed models and Spearman correlation analysis were used for statistical testing. RESULTS: 24 eyes of 17 laser-naive diabetic patients with different stages of DR were analyzed. The mean age was 59.56 ± 8.46 years and the mean disease duration 19.65 ± 12.25 years. No statistically significant associations between FAZ size, macular vessel density of SCP/DCP and peripheral retinal ischemia, leakage and MA number were demonstrated. Higher stages of DR were associated with ischemic index (estimate [95% CI]: 13.04 [1.5; 24.5], p = 0.033) and MA count (estimate [95% CI]: 43.7 [15.6; 71.8], p = 0.01), but no association with leakage index was observed. Only weak correlations between DR severity and anamnestic data were found. CONCLUSION: Retinal ischemic index and the amount of MAs assessed on UWFA up to peripheral areas are indicators of DR severity but not related to microvascular perfusion status in the macular region. Significance and timely sequence of macular vessel density in DR progression may need to be re-evaluated in future studies.

Posterior capsule opacification and Nd:YAG laser rates with two hydrophobic acrylic single-piece IOLs.

OBJECTIVES: To evaluate the development of posterior capsule opacification (PCO) and Nd:YAG capsulotomy rates following implantation of two hydrophobic acrylic IOLs. METHODS: In a randomized, controlled trial, 80 patients with bilateral senile cataract were implanted with the hydrophobic acrylic single-piece intraocular Lenses (IOLs) EyeCee One in one eye and iMics1 in the other. Outcomes of 39 patients (78 eyes) were evaluated after 3 years. Automated Quantification of After-Cataract (AQUA; for PCO occurrence), visual acuity, anterior fibrosis, capsule-optic edge interaction and distance between anterior and posterior capsule IOL surface were analysed. RESULTS: After a mean follow-up of 38 ± 1.95 months, Nd:YAG capsulotomy occurred at a rate of 15.4% and 46.2% in the EyeCee One and iMics1 groups, respectively (p < 0.01). Respective mean PCO scores measured by AQUA were 1.57 ± 1.63 and 2.45 ± 1.44 (p = 0.019). A distinct gap between the anterior capsule and the IOL optic was present in 89% of eyes implanted with EyeCee One and 13% of iMics1 eyes. A gap between the posterior capsule and the posterior surface of the lens was observed in 76% of EyeCee One eyes and 35% of iMics1 eyes. CONCLUSIONS: Study findings suggest that PCO and Nd:YAG capsulotomy rates are significantly lower in eyes implanted with the EyeCee One IOL compared to the iMics1 IOL. Optic sharpness and lens material seem to be the decisive factors, while the stepped edge beneath the haptic junction appeared to be ineffective.

Response of Retinal Sensitivity to Intravitreal Anti-angiogenic Bevacizumab and Triamcinolone Acetonide for Patients with Diabetic Macular Edema over One Year.

AIM: The aim of this study was to evaluate and compare microperimetry changes in patients with clinically significant diabetic macular edema secondary to diabetes mellitus, following intravitreal injections of bevacizumab or triamcinolone during a follow-up of 1 year after treatment. MATERIALS AND METHODS: 30 patients with clinically significant macular edema were randomized into two groups of 15 patients each. One group initially received three intravitreal injections of 2.5 mg bevacizumab at monthly intervals. The other received a single injection of 8 mg of triamcinolone followed by two sham interventions at monthly intervals. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were measured. Macular function was documented by microperimetry at baseline, 3, 6, 9 months and at the last visit of each patient. RESULTS: In the bevacizumab group, the mean differential light threshold (±standard deviation) under therapy improved significantly from 8.40 (± 3.8) dB to 12.8 (±4.3) dB at the 12-month follow-up visit (p ≤ .05), whereas in the triamcinolone group it increased from 8.0 (± 2.4) dB at baseline to 9.3 (±3.6) dB at the last visit without reaching statistical significance (p > .05). The mean differential light thresholds between the two groups were not statistically significant at baseline or the last visit (p > .05). In the bevacizumab group, the improvement (slope) in mean differential light threshold was significantly superior to the Triamcinolone group (Estimate = 0.588, p ≤ .05). CONCLUSION: Central macular function as measured by microperimetry in patients with acute DME improved in addition to anatomical restoration after intravitreal bevacizumab and triamcinolone injection. In our clinical study, the measures of the variables in patients receiving bevacizumab were superior to those receiving triamcinolone throughout the one-year observation period.

Optical coherence tomographic hyperreflective foci: a morphologic sign of lipid extravasation in diabetic macular edema.

PURPOSE: To analyze hyperreflective foci typically seen in diabetic macular edema (DME) in optical coherence tomography (OCT). DESIGN: Prospective clinical trial. PARTICIPANTS: Twelve consecutive patients with treatment-naïve, clinically significant DME. METHODS: During a same-day examination, a standardized visual acuity assessment (Early Treatment of Diabetic Retinopathy Study protocol), infrared fundus imaging, color fundus photography, and biomicroscopy were performed. Additionally, all patients were scanned using Stratus, Cirrus, and Spectralis OCT and results correlated. MAIN OUTCOME MEASURES: Morphologic changes secondary to DME. RESULTS: In all eyes with DME, distinct hyperreflective foci distributed throughout all retinal layers were found in the OCT scans of all 3 OCT devices. These deposits could not be identified by infrared imaging, fundus photography, or biomicroscopy as long as they were not confluent. Accumulations of such foci at the border of the outer nuclear and in the outer plexiform layer were recognizable clinically as hard exudates showing the same hyperreflective features in OCT. The hyperreflectivity of these foci did not correspond with intraretinal hemorrhage, nor did the lesions cause the characteristic OCT laser beam scattering phenomena typically seen secondary to intraretinal bleedings or microaneurysms. Further, they were detected within the walls of intraretinal microaneurysms. CONCLUSIONS: Well-demarcated, hyperreflective foci were identified in the retina of patients with DME. The deposits were located within walls of intraretinal microaneurysms and scattered throughout all retinal layers, forming confluent plaques in the outer plexiform layer. It is suggested that the foci represent extravasated lipoproteins and/or proteins being a very early subclinical barrier breakdown sign in DME.

Association of retinal sensitivity and morphology during antiangiogenic treatment of retinal vein occlusion over one year.

PURPOSE: Evaluation of the association between functional and anatomic retinal changes during anti-vascular endothelial growth factor (VEGF) therapy with bevacizumab (Avastin) in patients with cystoid macular edema secondary to retinal vein occlusion (RVO) using microperimetry and spectral domain optical coherence tomography (SD-OCT). DESIGN: Prospective, uncontrolled study (EUDRACT NR-2005-003288-21). PARTICIPANTS: Twenty-eight patients with cystoid macular edema secondary to RVO. METHODS: Patients initially received 3 consecutive intravitreal injections of 1.25 mg bevacizumab at 4-week intervals. Further treatment was based on morphologic (OCT) and functional best-corrected visual acuity (BCVA) findings. During the 1-year follow-up, a rigorous standardized evaluation was performed monthly. Macular function was documented by microperimetry (Nidek, MP1 Microperimeter) and BCVA based on the Early Treatment in Diabetic Retinopathy Study (ETDRS). Morphologic parameters included central retinal thickness (CRT) as measured by conventional OCT (Stratus), and central subfield thickness (CST), mean retinal thickness (MRT), and retinal volume (RV) measured by SD-OCT. MAIN OUTCOME MEASURES: Imaging of retinal morphology using OCT and SD-OCT and evaluation of retinal function assessed with microperimetry and ETDRS charts during 12 months of anti-VEGF treatment. RESULTS: Within 6 months, the mean area of absolute scotoma was reduced from 21.4% of the central visual field to 6.4% and remained at this level until month 12 (7.4%). Mean BCVA improved from 51 to 66 letters on ETDRS charts. The CRT, CST, and MRT decreased significantly (P<0.002) and remained stable during the follow-up. The RV values did not improve significantly under therapy. Statistical analysis using a linear effects model revealed significant associations between the functional and morphologic outcomes, most notably between BCVA, macular sensitivity, CRT (Stratus OCT), CST, and MRT (Cirrus OCT) values. CONCLUSIONS: Central retinal morphology, especially CRT and CST measured by conventional and SD-OCT, and retinal function improved significantly during treatment of RVO with a flexible dosing regimen of intravitreal bevacizumab. Functional (central visual acuity and visual field) and morphologic parameters (retinal thickness) were significantly related. These associations highlight the value of OCT imaging for assessing this disease entity.

Analysis of retinal layer thickness in diabetic macular oedema treated with ranibizumab or triamcinolone.

PURPOSE: To evaluate detailed changes in retinal layer thickness in spectral-domain optical coherence tomography (SD-OCT) images during a 1-year follow-up of patients treated for diabetic macula oedema (DME). METHODS: Post hoc analysis of retinal layer thickness changes applying the automated layer segmentation of SD-OCT images in eyes with DME that were randomly assigned to receive pro re nata (PRN) treatment with either 0.5 mg ranibizumab or 8 mg triamcinolone. In each patient, seven retinal layers were segmented in 49 scans covering a 20° × 20° area of the macula at baseline and after 1 year of treatment. Changes in individual layer thickness were correlated with visual acuity (VA) and compared between treatment arms. RESULTS: Twenty-five patients (seven female, 60.2 ± 15.1 years) were evaluated. Thickness decrease of retinal nerve fibre layer (RNFL) was associated with a gain in VA over 12 months (r > 0.54; p < 0.05). Decrease in ganglion cell layer (GCL) and GCL+IPL thickness pooled for nasal Early Treatment of Diabetic Retinopathy Study (ETDRS) subfields correlated with VA as follows: ranibizumab r = 0.74 (GCL) and r = 0.63 (GCL+IPL); and triamcinolone r = 0.45 (GCL) and r = 0.46 (GCL+IPL). CONCLUSION: In DME therapy, reduction in RNFL thickness may have a considerable impact on retinal function, unrelated to the type of pharmacological treatment. Precise morphologic quantification of neurosensory layers by SD OCT offers new insight into disease pathology and therapeutic targets.

Three-dimensional angiography of classic and occult lesion types in choroidal neovascularization.

PURPOSE: To identify characteristic features of classic and occult choroidal neovascularization (CNV) by using a novel technique of topographic angiography for three-dimensional (3D) visualization. METHODS: A confocal scanning laser ophthalmoscope (SLO, Heidelberg Retina Angiograph; Heidelberg Engineering, Dossenheim, Germany) was used to perform fluorescein (FA) and indocyanine green (ICGA) angiography in158 patients. Ninety-four eyes had predominantly classic and 64 eyes had occult lesions. With an image frequency of 20 Hz, a tomographic series of 32 images per set were taken over a depth of 4 mm. Axial analyses for each x/year position were performed, to determine the fluorescence distribution along the z-axis. After the axial location of hyperfluorescence was detected, a depth profile was generated. All results were integrated into a gray-scale-coded depth image and imaged as a 3D relief. RESULTS: Characteristic features of classic and occult lesions were distinguished. Classic CNV appeared as a well-demarcated lesion with steep, prominent borders, often craterlike, and frequently surrounded by a halo, suggesting choroidal perfusion changes. Occult CNV was documented by 3D as a convex lesion with flat, ill-defined borders and without any surrounding halo. Topographic imaging is superior to conventional angiography regarding definition of lesion type, configuration, and extension, because masking phenomena do not interfere. CONCLUSIONS: Topographic angiography allows a realistic 3D representation of CNV. Characteristic features based on the neovascular architecture and the differences in leakage behavior of different lesion types are clearly identified.