Recovery course of persistent posterior subretinal fluid after successful repair of rhegmatogenous retinal detachment.

PURPOSE: To investigate best corrected visual acuity (BCVA), subretinal fluid (SRF) absorption time or ellipsoid zone (EZ) restoration time and various variables in patients with persistent SRF after successful primary repair of rhegmatogenous retinal detachment (RRD). METHODS: This retrospective multicenter study allowed independent analysis of the healing pattern by two observers based on composite of serial cross-sectional macular optical coherence tomography (OCT) scans. Univariate and multivariate analyses were implemented. RESULTS: One hundred and three cases had persistent SRF after pars plana vitrectomy, scleral buckling, or pneumatic retinopexy. By univariate analysis, SRF resolution time correlated positively with the number of retinal breaks (p < 0.001) and with increased myopia (p = 0.011). Using multivariate analysis, final BCVA (log MAR) correlated positively with age, duration of RRD, initial BCVA (OR = 3.28; [95%CI = 1.44-7.47]; p = 0.015), and SRF resolution time (OR = 0.46 [95%CI 0.21-1.05]; p = 0.049). EZ restoration time was longer with increasing number of retinal tears (OR = 0.67; [95%CI 0.29-1.52]; p = 0.030), worse final BCVA, and presence of macula-off RRD (OR = 0.26; [95%CI 0.08-0.88]; p = 0.056). SRF resolution time correlated marginally with prone position. CONCLUSIONS: Residual posterior SRF is more common in eyes with multiple breaks or in myopic eyes. Final BCVA is better in younger subjects and in eyes with shorter duration of RRD. Persistent SRF is a self-limited disorder with a mean resolution of 11.2 months with good visual prognosis improving from a mean baseline logMAR of 1.08 to 0.25 at one year.

LIGHTSITE II Randomized Multicenter Trial: Evaluation of Multiwavelength Photobiomodulation in Non-exudative Age-Related Macular Degeneration.

INTRODUCTION: Photobiomodulation (PBM) represents a potential treatment for non-exudative age-related macular degeneration (AMD). PBM uses wavelengths of light to target components of the mitochondrial respiratory chain to improve cellular bioenergetic outputs. The aim of this study was to further investigate the effects of PBM on clinical, quality of life (QoL) and anatomical outcomes in subjects with intermediate stage non-exudative AMD. METHODS: The multicenter LIGHTSITE II study was a randomized clinical trial evaluating safety and efficacy of PBM in intermediate non-exudative AMD. The LumiThera Valeda® Light Delivery System delivered multiwavelength PBM (590, 660 and 850 nm) or sham treatment 3 × per week over 3-4 weeks (9 treatments per series) with repeated treatments at baseline (BL), 4 and 8 months. Subjects were enrolled with 20/32 to 20/100 best-corrected visual acuity (BCVA) and no central geographic atrophy (GA) within the central fovea (500 µm). RESULTS: LIGHTSITE II enrolled 44 non-exudative AMD subjects (53 eyes). PBM-treated eyes showed statistically significant improvement in BCVA at 9 months (n = 32 eyes, p = 0.02) with a 4-letter gain in the PBM-treated group versus a 0.5-letter gain in the sham-treated group (ns, p < 0.1) for patients that received all 27 PBM treatments (n = 29 eyes). Approximately 35.3% of PBM-treated eyes showed ≥ 5-letter improvement at 9 months. Macular drusen volume was not increased over time in the PBM-treated group but did show increases in the sham-treated group. While PBM and sham groups both showed GA lesion growth in the trial period, there was 20% less growth in the PBM group over 10 months, suggesting potential disease-modifying effects. No safety concerns or signs of phototoxicity were observed. CONCLUSION: These results confirm previous clinical testing of multiwavelength PBM and support treatment with Valeda as a novel therapy with a unique mechanism of action as a potential treatment for non-exudative AMD. TRIAL REGISTRATION: Clinicaltrial.Gov Registration Identifier: NCT03878420.

Endoscope-Assisted Carlevale Lens Implantation in Patients Without Capsular Support: A Novel Surgical Approach to Ensure Correct Lens Positioning.

PURPOSE: To describe endoscope-assisted Carlevale intraocular lens (IOL) implantation. METHODS: Twelve eyes underwent posterior vitrectomy combined with Carlevale IOL implantation and endoscopy in a single procedure, using a technique developed by the authors. Transscleral incisions were performed under direct visualization of the sulcus using the endoscope, and the final lens position was checked at the end of each intervention. The main outcome was to determine the exact position of all lens fixation points. RESULTS: All plugs were correctly placed in the sulcus, but in seven eyes (58.3%), at least one of the closed-loop haptics was folded over the ciliary body. Repositioning was performed during the same procedure. Given that each IOL has four closed-loop haptics, the incidence of this complication was 23% (11/48). CONCLUSION: Blind implantation of Carlevale IOL may cause a high incidence of haptic malpositioning. Because the sulcus and the ciliary body are not visible under the microscope, endoscopy is the only way to ensure correct lens implantation. This new technique ensures that all lens fixation points are correctly placed by the end of surgery, avoiding complications such as decentration or tilting of the IOL, damage to the iris or the ciliary body, and uveitis.

Recovery course of foveal microstructure in the nonsurgical resolution of full-thickness macular hole.

PURPOSE: To analyze the recovery course of foveal microstructures in eyes with nonsurgical healing of full-thickness macular hole (FTMH). METHODS: By serial OCT scans, the temporal healing sequences were analyzed in ocular trauma, vitreomacular traction (VMT), cystoid macular edema (CME), and the remaining group. We evaluated correlations between the final best-corrected spectacle visual acuity and reconstruction time of external limiting membrane (ELM), and inner segment/outer segment (IS/OS). RESULTS: The healing (mean±standard deviation in months) most involved fusion at the level of the outer nuclear layer (ONL) (6.3±10.5) followed by restoration of ELM (9.1±13.8), and lastly, by IS/OS regeneration (13.1±19.5). In severe blunt ocular trauma, healing was fast and involved subretinal zipper glue-like reapposition with resulting outer retinal atrophy. Best spectacle-corrected visual acuity correlated with normalization of the clivus (p=0.012), faster ELM (p=0.006), and IS/OS reconstitution (p=0.024). Recurrence of FTMH occurred when the healing was halted (3 eyes) or was aberrant by lamellar hole epiretinal proliferation (LHEP) (3 eyes) or by the persistence of VMT (1 eye). CONCLUSION: Recovery sequences proceeded from the ONL to the deeper layers with BCVA correlating absolutely and temporally with the restoration of outer retinal layer integrity.

Clinical characteristics of full thickness macular holes that closed without surgery.

PURPOSE: To ascertain the anatomic factors that help achieve non-surgical sealing in full thickness macular hole (FTMH). METHODS: Retrospective collaborative study of FTMH that closed without surgical intervention. RESULTS: A total of 78 patients (mean age 57.9 years) included 18 patients with blunt ocular trauma, 18 patients that received topical or intravitreal therapies and 42 patients with idiopathic FTMH. Mean±SD of the initial corrected visual acuity (VA) in logMAR improved from 0.65±0.54 to 0.34±0.45 (p<0.001) at a mean follow-up of 33.8±37.1 months. FTMH reopened in seven eyes (9.0%) after a mean of 8.6 months. Vitreomacular traction was noted in 12 eyes (15.8%), perifoveal posterior vitreous detachment in 42 (53.8%), foveal epiretinal membrane in 10 (12.8%), cystoid macular oedema (CME) in 49 (62.8%) and subretinal fluid (SRF) in 20 (25.6%). By multivariate analysis, initial VA correlated to the height (p<0.001) and narrowest diameter of the hole (p<0.001) while final VA correlated to the basal diameter (p<0.001). Time for closure of FTMH (median 2.8 months) correlated to the narrowest diameter (p<0.001) and the presence of SRF (p=0.001). Mean time for closure (in months) was 1.6 for eyes with trauma, 4.3 for eyes without trauma but with therapy for CME, 4.4 for eyes without trauma and without therapy in less than 200 µm in size and 24.7 for more than 200 µm. CONCLUSION: Our data suggest an observation period in new onset FTMH for non-surgical closure, in the setting of trauma, treatment of CME and size <200 µm.

Ab externo approach to treat bilateral haptic extrusion secondary to scleral erosion of an intrascleral sutureless-fixated intraocular lens.

Surgical management of haptic extrusion of an intrascleral sutureless-fixated intraocular lens (IOL) (FIL-SSF Carlevale, Soleko) by repositioning the IOL without lens extraction was reported. The patient presented an early extrusion of both IOL harpoons just 4 weeks after the initial surgery. New scleral flaps were created 30 degrees superior to the nasal harpoon and 30 degrees inferior to the temporal harpoon so that the IOL was rotated clockwise. Each haptic was grasped with a 25-gauge forceps and introduced into the vitreous cavity and regrasped with another forceps through a new port, 1.5 mm posterior to the limbus, and underneath a new scleral flap. The Carlevale IOL is specially designed for sutureless intrascleral fixation with excellent anatomic and visual results but may also show specific complications. To the authors' knowledge, this is the first report on how to efficiently manage harpoon erosion using this simple technique.

Swept source optical coherence tomography angiography in patients treated with hydroxychloroquine: correlation with morphological and functional tests.

PURPOSE: To evaluate swept source optical coherence tomography angiography (SS-OCTA) in patients treated with hydroxychloroquine (HCQ) for more than 5 years and to compare results with the tests currently recommended for screening of HCQ retinopathy. METHODS: In this controlled pilot study, consecutive patients treated with HCQ for more than 5 years underwent SS-OCTA, SS-OCT B-scan and en-face C-scan, fundus autofluorescence (FAF), 10-2 automated visual field (AVF) testing and multifocal electroretinography (mfERG). On SS-OCTA, evaluation of the retinal superficial capillary plexus, middle capillary plexus, and deep capillary plexus (DCP) and the choriocapillaris (CC) was obtained. RESULTS: We included 10 patients under HCQ treatment (20 eyes, mean age 38.91±11.73 years) and 18 healthy control patients (36 eyes, mean age 38.87±8.6 years). Mean duration of HCQ treatment was 10.0±3.25 (5-15) years and HCQ cumulative dose/body weight was 15.86±5.56 g/kg. The HCQ group showed a reduction of the vessel density in the 1 mm central, in the nasal and temporal subfields of DCP and in the 1 mm central subfield of CC, an increased foveal avascular zone in the three capillary plexuses, a greater frequency of CC flow voids and a reduced foveal choroidal thickness (p<0.05). Best-corrected visual acuity (BCVA), mfERG, SS-OCT B-scan and C-scan, AVF and FAF were normal in 20/20 eyes (100%). CONCLUSIONS: In patients treated with HCQ for more than 5 years, choroidal thinning and flow abnormalities at SS-OCTA in the retinal capillary plexuses and CC may be observed even if BCVA, FAF, mfERG, AVF and SS-OCT are normal.

QUANTITATIVE AND QUALITATIVE ANALYSIS OF THE THREE CAPILLARY PLEXUSES AND CHORIOCAPILLARIS IN PATIENTS WITH TYPE 1 AND TYPE 2 DIABETES MELLITUS WITHOUT CLINICAL SIGNS OF DIABETIC RETINOPATHY: A Prospective Pilot Study.

PURPOSE: To separately evaluate the three retinal capillary plexuses and the choriocapillaris in patients with diabetes mellitus (DM) Type 1 and Type 2, without clinical signs of diabetic retinopathy. METHODS: The study was prospective and cross-sectional. Only patients with age ≤55 years were included. We used a swept-source optical coherence tomography angiography device (Triton; Topcon, Tokyo, Japan) to obtain both quantitative and qualitative analysis of the retinal capillary plexuses (superficial capillary plexus; middle capillary plexus; and deep capillary plexus) and the choriocapillaris. RESULTS: We included 17 patients with DM Type 1 (age 34.52 ± 11.05 years, 29 eyes), 17 patients with DM Type 2 (age 48.76 ± 3.26 years, 32 eyes), and 23 healthy control subjects (age 41.82 ± 8.97 years, 43 eyes). When compared with controls, vessel density in the central 1 mm was reduced in both DM Type 1 and DM Type 2 groups in the superficial capillary plexus (P = 0.05 and P = 0.02, respectively), and in DM Type 2 in the deep capillary plexus (P = 0.03). Foveal avascular zone was increased in the middle capillary plexus and deep capillary plexus of DM Type 2 group compared with controls (P = 0.03 and P = 0.02, respectively). Choriocapillary voids were more frequent in DM Type 1 and DM Type 2 compared with controls (P = 0.003 and P < 0.001, respectively). CONCLUSION: Microvascular modifications are present in the three retinal capillary plexuses and the choriocapillaris in both DM Type 1 and DM Type 2 even in the absence of clinical signs of diabetic retinopathy.

OUTCOME OF ACUTE NONTRAUMATIC VITREOUS HEMORRHAGE IN HEALTHY PATIENTS.

PURPOSE: To compare outcomes in dense vitreous hemorrhage versus mild vitreous hemorrhage due to nontraumatic posterior vitreous detachment. METHODS: We compared 315 eyes, divided into 2 patient groups, one with dense and the other with mild vitreous hemorrhage. The main outcome measures were final mean best-corrected visual acuity, number of retinal tears, number of retinal detachments, and the number of pars plana vitrectomy and/or scleral buckle surgeries. RESULTS: In 33.4% of the patients, posterior vitreous detachment without complications was found. Retinal breaks after posterior vitreous detachment were found in 59% of the eyes. Rhegmatogenous retinal detachment was principally treated with pars plana vitrectomy and scleral buckle. In nonvisible fundus hemorrhage group, 44.4% of the patients underwent vitrectomy. In visible fundus hemorrhage group, 9.52% of the patients underwent pars plana vitrectomy. The mean final visual acuity was 20/25, without significant difference between groups (P = 0.064). CONCLUSION: Acute, spontaneous, nontraumatic posterior vitreous separation with vitreous hemorrhage is associated with a high incidence of retinal complications. Close follow-up is necessary. We did not find significant differences in final visual acuity neither between the two groups nor among the treatments.

Successful Treatment of a Retinal Detachment Secondary to Multiple Eccentric Macular Holes With Autologous Lens Capsular Flap Transplantation.

The authors report a case of a retinal detachment secondary to multiple eccentric macular holes (MEMHs) following an uneventful pars plana vitrectomy and epiretinal membrane peel, successfully treated by autologous lens capsule graft. Anatomical and functional changes were also evaluated. Autologous lens capsule graft is a safe and effective treatment for MEMHs that may improve anatomical and functional results. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:901-903.].

Visual outcome and complications of cataract extraction after pars plana vitrectomy.

PURPOSE: To evaluate the visual outcomes and complications of phacoemulsification in previously vitrectomized eyes. PATIENTS AND METHODS: A retrospective analysis of 87 consecutive vitrectomized eyes (87 patients) which had undergone phacoemulsification with intraocular lens implantation between 2013 and 2016. RESULTS: The mean interval from pars plana vitrectomy (PPV) to cataract surgery (CS) was 18.8 months. Mean age at CS was 61.5 years. Intraoperative complications included anterior rhexis tear (1 eye) and hyphema (1 eye). Postoperative complications included macular edema (17.2%, mean 42 days), posterior capsule opacification (13.8%, mean 14 months), ocular hypertension (11.5%), and anterior uveitis (1.1%). Preoperative mean best-corrected visual acuity improved from 20/50 to 20/25. Ninety-one percent of the eyes gained 2 or more lines, and 95% achieved visual acuity ≥20/40 after CS. Preoperative mean spherical equivalent improved from -4.35 to -0.17. Eyes with clear lens prior to the PPV had later CS (clear lens 27.1 vs no clear lens 9.7 months; p=0.016). Patients >55 years with clear lens at PPV (n=21) had earlier CS than younger ones with clear lens (n=24) (11.8 vs 40.5 months; p=0.033). Mean follow-up was 14.5 months. CONCLUSION: Phacoemulsification is a safe procedure in vitrectomized eyes, with substantial gains in vision in most cases. Patients of advanced age and eyes without clear lens prior to the PPV had earlier CS.

ASSESSMENT OF THE INTERNAL LIMITING MEMBRANE STATUS WHEN A MACULAR EPIRETINAL MEMBRANE IS REMOVED IN A PROSPECTIVE STUDY.

PURPOSE: To describe the presence and integrity of the internal limiting membrane (ILM) after removal of the macular epiretinal membrane (ERM) and to investigate the accuracy of tissue identification using surgical dyes when compared to histopathology results. METHODS: Patients with idiopathic ERM were enrolled in a prospective study and randomized to one of two surgical techniques. In one (Group M), only the ERM was deliberately removed and in the other (Group L) the ILM was also removed. Pars plana vitrectomy and extraction of the ERM with trypan blue dye were performed in all patients. The ILM status was assessed with brilliant blue G dye, and in Group L patients, the ILM was then removed. Histopathology was performed on all samples. RESULTS: Twenty-six patients underwent the study procedure: 11 in the Group M and 15 in the Group L. The patients' median age was 70.65 years (53-81), and the average follow-up was 15.35 months (4.86-25.10). The ILM extraction patterns were as follows: In Group M in block in 8 of 11 patients and partial in 3 of 11 patients; In Group L in block in 9 of 15 patients, partial in 5 of 15 patients and sequential in 1 of 15 patients. In only 3.8% of patients was the ILM intact after ERM removal. Thirty-two surgical samples were analyzed, containing both ERM and ILM, ERM only, or ILM only. In 84.37% of samples, the tissue identification using surgical dyes was consistent with identification according to pathological examination. This consistency was higher still at 96.7% when focused on ILM identification. CONCLUSION: It is technically difficult to extract the ERM in isolation from the ILM. There is good consistency between the content of removed tissue as identified using surgical dyes and the histopathological results of the samples. This is higher in ILM than in ERM.

Subfoveal choroidal thickness changes in carotid cavernous fistula following spontaneous resolution.

BACKGROUND: We report the enhanced depth imaging optical coherence tomography (EDI-OCT) characteristics and variations in a patient with subretinal fluid secondary to a carotid cavernous fistula. CASE PRESENTATION: A 59-year-old man presented with blurred vision in his right eye. Venous congestion of the epiescleral and retinal vessels were observed. EDI-OCT disclosed macular subretinal fluid with an increase of choroidal thickness up to 341 µm. Brain and orbital computerized tomography showed an enlarged right superior ophthalmic vein. Orbital magnetic resonance imaging and angiography disclosed a decrease in blood flow, an indirect sign of carotid cavernous fistula. After a 3 months follow-up, spontaneous closure of the fistula occurred. Both the dilation of the conjunctiva and retinal veins improved. EDI-OCT showed resolution of the subfoveal fluid and a reduction of the subfoveal choroidal thickness to 271 µm after a 3 months follow-up and 168 µm after a 8 months follow-up. CONCLUSION: Serous retinal detachment has been described as a rare complication of carotid cavernous fistula. In our patient, EDI-OCT examinations revealed a thicker choroidal thickness when subretinal fluid was present as compared to that observed in the contralateral eye or after subretinal fluid resolution.

SURGICAL OUTCOME OF LATE IN-THE-BAG INTRAOCULAR LENS DISLOCATION TREATED WITH PARS PLANA VITRECTOMY.

PURPOSE: To present the visual outcome and postoperative complications of pars plana vitrectomy and intraocular lenses (IOL) removal with or without IOL exchange of late in-the-bag IOL dislocation after uneventful cataract surgery. METHODS: Retrospective analysis of a consecutive series of 83 eyes with late in-the-bag dislocated IOL treated with pars plana vitrectomy and anterior chamber IOL (25 eyes), transscleral suture-fixated posterior chamber IOL (38 eyes), or aphakia (20 eyes). RESULTS: High myopia was the major predisposing factor (40%). The interval between cataract surgery and the dislocation was 10.9 years. The complication rate after the second surgery was 43%; being transient hypotony (19%) and hypertension (15%) the most frequent. Postoperative best-corrected visual acuity improvement was statistically significant (P < 0.001), with a mean of 3 Snellen lines. This improvement was also significant in 2 subgroups, patients with sutured posterior chamber IOL (20/80-20/40; P < 0.001) and in patients with anterior chamber IOL (20/125-20/40; P < 0.001). However, best-corrected visual acuity did not improve in aphakic patients (20/63-20/63; P = 0.13). Postoperative astigmatism increased significantly (P < 0.001), with a mean of -1 D. Mean follow-up was 24 months. CONCLUSION: The major predisposing factor for late in-the-bag IOL dislocation is myopia. Despite a complication rate of 43%, mostly minor and transient, IOL exchange surgery is an effective procedure with a good visual outcome (mean 3 Snellen lines improvement). There were no statistically significant differences in the final best-corrected visual acuity or complication rate between anterior chamber IOL and sutured posterior chamber IOL, thus, both surgical techniques may be considered to treat this condition.

Relevance of Retinal Thickness Changes in the OCT Inner and Outer Rings to Predict Progression to Clinical Macular Edema: An Attempt of Composite Grading of Macular Edema.

PURPOSE: To characterize the relevance of macular thickness changes in the inner and outer rings in the progression of macular edema in eyes/patients with diabetes type 2. METHODS: A total of 374 type 2 diabetic patients with mild nonproliferative diabetic retinopathy (ETDRS levels 20-35) were included in a 12-month prospective observational study to identify retinopathy progression. Retinal thickness analyses were performed in 194 eyes/patients using Cirrus SD- OCT and 166 eyes/patients using Spectralis SD-OCT. The DRCR.net classification of subclinical and clinical macular edema was used. A composite grading of macular edema is proposed in this study. RESULTS: A total of 317 eyes/patients completed the study. SD-OCT identified clinical macular edema in 24 eyes/patients (6.7%) and subclinical macular edema in 104 eyes/patients (28.9%) at baseline. Increased thickness of the central subfield is the best predictor for the development of clinical macular edema, with 85.7% sensitivity and 71.9% specificity (OR: 2.57, 95% CI: 0.82-7.99). However, the involvement of the inner and outer rings is a cumulative predictor of progression to clinical macular edema (OR: 8.69, 95% CI: 2.85-26.52). CONCLUSIONS: A composite OCT grading of macular edema taking into account the retinal thickness changes in the inner and outer macular rings offers a simple way to characterize macular edema, with added clinical value.

Characterization of Retinal Disease Progression in a 1-Year Longitudinal Study of Eyes With Mild Nonproliferative Retinopathy in Diabetes Type 2.

PURPOSE: To identify eyes of patients with diabetes type 2 that show progression of retinal disease within a 1-year period using noninvasive techniques. METHODS: Three hundred seventy-four type 2 diabetic patients with mild nonproliferative diabetic retinopathy (Early Treatment Diabetic Retinopathy Study [ETDRS] level 20 or 35) were included in a 12-month prospective observational study to identify retinopathy progression. Four visits were scheduled at 0, 3, 6, and 12 months. Microaneurysm (MA) activity using the RetmarkerDR and retinal thickness using spectral-domain optical coherence tomography (SD-OCT) were assessed by a central reading center at all visits and ETDRS severity level in the first and last visits. RESULTS: Three hundred thirty-one eyes/patients completed the study. Microaneurysm formation rate greater than or equal to 2 was present in 68.1% of the eyes and MA turnover greater than or equal to 6 in 54.0% at month 6. Higher MA turnover values were registered in eyes that showed progression in ETDRS severity level (P < 0.03). There were also significant correlations between increased microaneurysm activity and increases in retinal thickness. Spectral-domain OCT identified clinical macular edema in 24 eyes/patients (6.7%) and subclinical macular edema in 104 eyes/patients (28.9%) at baseline. Progression of retinal thickening was registered in eyes that had either subclinical or clinical macular edema at baseline. CONCLUSIONS: Changes in MA activity measured with RetmarkerDR and in central retinal thickness in eyes with mild nonproliferative diabetic retinopathy and diabetes type 2 are able to identify eyes at risk of progression. These eyes/patients should be selected for inclusion in future clinical trials of drugs targeted to prevent diabetic retinopathy progression to vision-threatening complications. (ClinicalTrials.gov number, NCT01145599.)

Retinal layer location of increased retinal thickness in eyes with subclinical and clinical macular edema in diabetes type 2.

PURPOSE: To identify the retinal layer predominantly affected in eyes with subclinical and clinical macular edema in diabetes type 2. METHODS: A cohort of 194 type 2 diabetic eyes/patients with mild nonproliferative diabetic retinopathy (ETDRS levels 20/35) were examined with Cirrus spectral-domain optical coherence tomography (OCT) at the baseline visit (ClinicalTrials.gov identifier: NCT01145599). Automated segmentation of the retinal layers of the eyes with subclinical and clinical macular edema was compared with a sample of 31 eyes from diabetic patients with normal OCT and an age-matched control group of 58 healthy eyes. RESULTS: From the 194 eyes in the study, 62 had subclinical macular edema and 12 had clinical macular edema. The highest increases in retinal thickness (RT) were found in the inner nuclear layer (INL; 33.6% in subclinical macular edema and 81.8% in clinical macular edema). Increases were also found in the neighboring layers. Thinning of the retina was registered in the retinal nerve fiber, ganglion cells and inner plexiform layers in the diabetic eyes without macular edema. CONCLUSIONS: The increase in RT occurring in diabetic eyes with macular edema is predominantly located in the INL but extends to neighboring retinal layers indicating that it may be due to extracellular fluid accumulation.