Long-Term Follow-Up of Patients with Scleritis After Rituximab Treatment Including B Cell Monitoring.

PURPOSE: We report the long-term effect of rituximab (RTX) in scleritis and determine the value of B-cell monitoring for the prediction of relapses. METHODS: We retrospectively studied 10 patients with scleritis, who were treated with RTX. Clinical characteristics were collected, and blood B-cell counts were measured before the start of RTX, and at various time points after treatment. RESULTS: Clinical activity of scleritis decreased after RTX treatment in all patients within a median time of 8 weeks (range 3-13), and all reached remission. The median follow-up was 101 months (range 9-138). Relapses occurred in 6 out of 10 patients. All relapses, where B-cell counts were measured (11 out of 19), were heralded by returning B cells. However, B cells also returned in patients with long-term remissions. CONCLUSIONS: RTX is a promising therapeutic option for scleritis. Recurrence of B cells after initial depletion does not always predict relapse of scleritis.

Long-Term Follow-up of Patients With Uveitis Treated With Adalimumab: Response Rates and Reasons for Discontinuation of Therapy.

PURPOSE: To evaluate the effectiveness and reasons for discontinuation including the side effect profiles of adalimumab in a real-world setting. DESIGN: Retrospective clinical cohort study. METHODS: A medical chart review of clinical practice in 2 tertiary eye care services in Rotterdam, the Netherlands, was performed Data were collected from May 1, 2004, through September 1, 2020. Patients with noninfectious uveitis treated with adalimumab (n = 341; 633 affected eyes) were included. The primary outcome was the effectiveness of adalimumab, measured by the number of patients achieving inactive disease, remission, and relapse-free survival. The secondary outcomes were the reasons for discontinuation, including side effects, and the number of patients who developed antibodies. RESULTS: In total, 341 patients were treated with adalimumab between May 2004 and September 2020. The uveitis recurrence-free survival interval was 3.4 years (range, 0-13 years). Adalimumab had an acceptable side effect profile. A total of 178 patients achieved inactive disease while continuing adalimumab, and 51 patients maintained remission after discontinuing adalimumab. Reasons for discontinuation of adalimumab were no response, relapse, or reasons unrelated to the effectiveness of treatment. Adalimumab antibodies were present in 40 of 115 patients (35%). Antibodies were associated with lower adalimumab levels, and antibodies were observed more often in patients on adalimumab monotherapy (P < .01). CONCLUSIONS: Adalimumab is effective for patients with noninfectious uveitis, with an acceptable side effect profile. Although relapses can occur, the majority of the patients achieved inactive disease or remission after cessation of adalimumab, without other systemic immunosuppressive medication.

Vitreous proteomics, a gateway to improved understanding and stratification of diverse uveitis aetiologies.

PURPOSE: The vitreous proteome might provide an attractive gateway to discriminate between various uveitis aetiologies and gain novel insights into the underlying pathophysiological processes. Here, we investigated 180 vitreous proteins to discover novel biomarkers and broaden disease insights by comparing (1). primary vitreoretinal lymphoma ((P)VRL) versus other aetiologies, (2). sarcoid uveitis versus tuberculosis (TB)-associated uveitis and (3). granulomatous (sarcoid and TB) uveitis versus other aetiologies. METHODS: Vitreous protein levels were determined by proximity extension assay in 47 patients with intraocular inflammation and a prestudy diagnosis (cohort 1; training) and 22 patients with a blinded diagnosis (cohort 2; validation). Differentially expressed proteins identified by t-tests on cohort 1 were used to calculate Youden's indices. Pathway and network analysis was performed by ingenuity pathway analysis. A random forest classifier was trained to predict the diagnosis of blinded patients. RESULTS: For (P)VRL stratification, the previously reported combined diagnostic value of IL-10 and IL-6 was confirmed. Additionally, CD70 was identified as potential novel marker for (P)VRL. However, the classifier trained on the entire cohort (cohort 1 and 2) relied primarily on the interleukin score for intraocular lymphoma diagnosis (ISOLD) or IL-10/IL-6 ratio and only showed a supportive role for CD70. Furthermore, sarcoid uveitis displayed increased levels of vitreous CCL17 as compared to TB-associated uveitis. CONCLUSION: We underline the previously reported value of the ISOLD and the IL-10/IL-6 ratio for (P)VRL identification and present CD70 as a potentially valuable target for (P)VRL stratification. Finally, we also show that increased CCL17 levels might help to distinguish sarcoid uveitis from TB-associated uveitis.

Parafoveal Microvascular Alterations in Ocular and Non-Ocular BehÒ«et's Disease Evaluated With Optical Coherence Tomography Angiography.

Purpose: To compare quantitative optical coherence tomography angiography (OCT-A) measurements of the parafoveal microvasculature in retinal capillary plexuses among BehÒ«et uveitis (BU) patients, non-ocular BehÒ«et's disease (NOBD) patients, and healthy volunteers (HVs). Methods: Sixty-eight subjects were enrolled in this prospective observational cross-sectional study. OCT-A imaging was performed using the Heidelberg Engineering Spectralis OCT. A custom algorithm was developed to calculate the vessel density (VD) in three retinal vascular layers: deep capillary plexus, intermediate capillary plexus, and superficial vascular plexus. The foveal avascular zone (FAZ) and acircularity index were calculated for the whole retinal vascular complex. Results: We analyzed one eye from 21 BU patients (age, 51 ± 10 years), 23 NOBD patients (age, 48 ± 14 years), and 22 HVs (age, 44 ± 13 years). One-way multivariate analysis of covariance showed a statistically significant difference in VD among the three groups when combining the layers after controlling for scan quality (P < 0.001). The VD was lowest in the BU group and highest in the HV group in all layers. The FAZ area was also statistically significant different among the groups (P < 0.005), with the largest FAZ areas in BU patients and smallest FAZ areas in the HV group. However, no statistically significant difference was found for the acircularity index. Conclusions: The parafoveal microvasculature is affected not only in BU patients but also in NOBD patients. Most deviations in the retinal microcirculation in BehÒ«et patients were found in the deeper layers of the retina by using the quantitative VD measurement.

Intra- and Intergrader Agreement for Detection of OCT Angiographic Characteristics Associated With Type 3 Neovascularization.

Purpose: To examine the intra- and intergrader agreement on morphologic characteristics of type 3 neovascularization on optical coherence tomography angiography (OCT-A). Methods: OCT-A images of 22 eyes from 21 patients with a new-onset, treatment-naive type 3 neovascularization were included in this cross-sectional retrospective agreement study. Each image was graded three times by two independent medical retina specialists to assess intra- and intergrader agreement. The graders scored the presence or absence of the following vascular and structural features: intraretinal neovascularization (IRN), subretinal neovascularization, sub-retinal pigment epithelium (RPE) neovascularization (SRPEN), retinal choroidal anastomosis (RCA), intraretinal cysts, subretinal fluid, and pigment epithelial detachment. Agreement was analyzed for each feature using Gwet's AC1, к statistics, and percentage of agreement. Results: The best agreement (AC1) was found for intraretinal neovascularization (withingrader1: 0.94; withingrader2: 0.93 and between: 1.00) and intraretinal cysts (withingrader1, 1.00; withingrader2, 0.97 and between, 1.00). The poorest intragrader agreements were observed for SRPEN (withingrader1, 0.54 and withingrader2, 0.36) and RCA (withingrader1, 0.45 and withingrader2, 0.52), and the poorest intergrader agreement was found for SRPEN, RCA, and pigment epithelial detachment (0.18, 0.37, and 0.15, respectively). Conclusions: Although the agreement values were high for intraretinal features, considerable grader variability was found for the vascular and structural features in the deeper retina or under the RPE. Clinicians should be careful to base therapeutic decisions on qualitative OCT-A assessment, because even well-trained specialists show a considerable grader variation in their subjective evaluation. Translational Relevance: The clinical value of OCT-A imaging largely depends on the agreement of subjective evaluations by ophthalmologists.

Detailed optical coherence tomography angiographic short-term response of type 3 neovascularization to combined treatment with photodynamic therapy and intravitreal bevacizumab.

PURPOSE: To explore the short-term vascular and structural changes of type 3 neovascularization using optical coherence tomography angiography (OCT-A) when treated with a combination of photodynamic therapy (PDT) and intravitreal bevacizumab (IVB), and to evaluate the course of different sequences of the combined therapies. METHODS: Thirty eyes of 29 treatment-naïve patients with a type 3 neovascularization were included in this prospective observational cohort study. They were all treated with PDT and IVB 2 weeks apart, starting either with PDT (PDT-first group) or IVB (IVB-first group). Optical coherence tomography angiography (OCT-A) imaging was performed at week 0, 2, 4 and 18, and best corrected visual acuity (BCVA) at week 0 and 18. Vascular, structural and functional features were graded and analysed over time. RESULTS: In all patients, at all follow-up visits, vascular and structural features were significantly more often decreased or resolved than unchanged or increased. Best corrected visual acuity (BCVA) significantly improved at 18 weeks. Vascular, structural and functional outcomes were all slightly better in the PDT-first group compared to the IVB-first group, although not statistically significant. CONCLUSION: Combined treatment of PDT and IVB is effective in short-term for type 3 neovascularization based on vascular and structural features. Initial treatment with PDT tended to be more effective than with IVB.

Long-Term Safety and Efficacy of Adalimumab in Patients with Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis.

PURPOSE: To evaluate long-term efficacy and safety of extended treatment with adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. DESIGN: Open-label, multicenter, phase 3 extension study (VISUAL III). PARTICIPANTS: Adults who had completed a randomized, placebo-controlled phase 3 parent trial (VISUAL I or II) without treatment failure (inactive uveitis) or who discontinued the study after meeting treatment failure criteria (active uveitis). METHODS: Patients received subcutaneous adalimumab 40 mg every other week. Data were collected for ≤ 362 weeks. Adverse events (AEs) were recorded until 70 days after the last dose. MAIN OUTCOME MEASURES: Long-term safety and quiescence; other efficacy variables included inflammatory lesions, anterior chamber cell and vitreous haze grade, macular edema, visual acuity, and dose of uveitis-related systemic corticosteroids. RESULTS: At study entry, 67% of patients (283/424) showed active uveitis and 33% (141/424) showed inactive uveitis; 60 patients subsequently met exclusion criteria, and 364 were included in the intention-to-treat analysis. Efficacy variables were analyzed through week 150, when approximately 50% of patients (214/424) remained in the study. Patients showing quiescence increased from 34% (122/364) at week 0 to 85% (153/180) at week 150. Corticosteroid-free quiescence was achieved by 54% (66/123) and 89% (51/57) of patients with active or inactive uveitis at study entry. Mean daily dose of systemic corticosteroids was reduced from 9.4 ± 17.1 mg/day at week 0 (n = 359) to 1.5 ± 3.9 mg/day at week 150 (n = 181). The percentage of patients who achieved other efficacy variables increased over time for those with active uveitis at study entry and was maintained for those with inactive uveitis. The most frequently reported treatment-emergent AEs of special interest were infections (n = 275; 79 events/100 patient-years [PY]); AEs and serious AEs occurred at a rate of 396 events/100 PY and 15 events/100 PY, respectively. CONCLUSIONS: Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and led to maintenance of quiescence for those with inactive uveitis. AEs were comparable with those reported in the parent trials and consistent with the known safety profile of adalimumab.

Classification and treatment follow-up of a juxtapapillary retinal hemangioblastoma with optical coherence tomography angiography.

PURPOSE: Only an endophytic growth pattern in juxtapapillary retinal hemangioblastoma (JRH) is an indication for surgical treatment, but classification of growth types is difficult using conventional imaging techniques. This case report describes the use of optical coherence tomography angiography (OCT-A) features for classification and treatment follow-up in a case with JRH. OBSERVATIONS: The JRH of this patient was easily detected with two different OCT-A methods in both en-face and cross-sectional B-scan images, and was classified as a sessile growth type. This growth type excluded the treatment option of vitreoretinal surgery with excision of the lesion or ligation of the feeder vessels. The patient was treated multiple times with intravitreal bevacizumab. Treatment follow-up with OCT-A initially revealed a stable extent of the JRH, with some slight flow deviations in en-face visualization, followed by a period of progressive growth of the lesion. CONCLUSIONS: OCT-A revealed the depth localization of the JRH and seems to be a valuable tool for JRH classification. Detailed classification may be useful when surgery is considered as a treatment strategy. Furthermore, treatment follow-up is possible with OCT-A, although imaging artifacts should be taken into account.

Treatment Effects in Retinal Angiomatous Proliferation Imaged with OCT Angiography.

PURPOSE: This prospective case series is aimed at exploring optical coherence tomographic angiography (OCT-A) as a treatment monitoring tool in patients treated for retinal angiomatous proliferation (RAP). METHODS: Twelve treatment-naïve RAP patients were included, with a median age of 79 years (range 65-90). Patients were imaged with an experimental 1,040-nm swept-source phase-resolved OCT-A instrument before and after treatment. Treatment consisted of either intravitreal bevacizumab or triamcinolone injections with or without photodynamic therapy (PDT). Abnormal blood flow after treatment was graded as increased, unchanged, decreased, or resolved. RESULTS: OCT-A images before and after treatment could be obtained in 9 patients. The median follow-up period was 10 weeks (range 5-19). After various treatments, the RAP lesion resolved in 7 patients, in 1 patient the OCT-A depicted decreased flow in the lesion, and 1 patient showed unchanged abnormal blood flow. Monotherapy with intravitreal bevacizumab injections resolved RAP in 1 out of 2 patients. Combined therapy of bevacizumab with PDT resolved RAP in 6 out of 7 patients. CONCLUSIONS: OCT-A visualized resolution of abnormal blood flow in 7 out of 9 RAP patients after various short-term treatment sequences. OCT-A may become an important noninvasive monitoring tool for optimizing treatment strategies in RAP patients.

Safety and Efficacy of Adalimumab in Patients with Noninfectious Uveitis in an Ongoing Open-Label Study: VISUAL III.

PURPOSE: To evaluate safety and efficacy of adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. DESIGN: Phase 3, open-label, multicenter clinical trial extension (VISUAL III). PARTICIPANTS: Adults meeting treatment failure (TF) criteria or who completed VISUAL I or II (phase 3, randomized, double-masked, placebo-controlled) without TF. METHODS: Patients received adalimumab 40 mg every other week. Interim follow-up data were described from VISUAL III weeks 0 through 78. MAIN OUTCOME MEASURES: Disease quiescence, steroid-free quiescence, active inflammatory chorioretinal/retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, best-corrected visual acuity (BCVA), and corticosteroid dose. Binary data were reported using nonresponder imputation (NRI), continuous data using last observation carried forward and as-observed analysis, and corticosteroid dose using observed-case analysis. Adverse events (AEs) were reported from first adalimumab dose in VISUAL III through interim cutoff. RESULTS: Of 424 patients enrolled, 371 were included in intent-to-treat analysis. At study entry, 242 of 371 (65%) patients had active uveitis; 60% (145/242, NRI) achieved quiescence at week 78, and 66% (95/143, as-observed) of those were corticosteroid free. At study entry, 129 of 371 (35%) patients had inactive uveitis; 74% (96/129, NRI) achieved quiescence at week 78, and 93% (89/96, as-observed) of those were corticosteroid free. Inflammatory lesions, anterior chamber grade, and vitreous haze grade showed initial improvement followed by decline in patients with active uveitis and remained stable in patients with inactive uveitis. BCVA improved in patients with active uveitis from weeks 0 to 78 (0.27 to 0.14 logMAR; left and right eyes; as-observed) and remained stable in patients with inactive uveitis. Mean corticosteroid dose decreased from 13.6 mg/day (week 0) to 2.6 mg/day (week 78) in patients with active uveitis and remained stable in those with inactive uveitis (1.5-1.2 mg/day). AEs (424 events/100 patient-years) and serious AEs (16.5 events/100 patient-years) were comparable with previous VISUAL trials. CONCLUSIONS: Patients with active uveitis at study entry who received adalimumab therapy were likely to achieve quiescence, improve visual acuity, and reduce their daily uveitis-related systemic corticosteroid use. Most patients with inactive uveitis at study entry sustained quiescence without a systemic corticosteroid dose increase. No new safety signals were identified.

Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus.

Diabetic retinopathy (DR) has long been recognized as a microvasculopathy, but retinal diabetic neuropathy (RDN), characterized by inner retinal neurodegeneration, also occurs in people with diabetes mellitus (DM). We report that in 45 people with DM and no to minimal DR there was significant, progressive loss of the nerve fiber layer (NFL) (0.25 µm/y) and the ganglion cell (GC)/inner plexiform layer (0.29 µm/y) on optical coherence tomography analysis (OCT) over a 4-y period, independent of glycated hemoglobin, age, and sex. The NFL was significantly thinner (17.3 µm) in the eyes of six donors with DM than in the eyes of six similarly aged control donors (30.4 µm), although retinal capillary density did not differ in the two groups. We confirmed significant, progressive inner retinal thinning in streptozotocin-induced "type 1" and B6.BKS(D)-Lepr(db)/J "type 2" diabetic mouse models on OCT; immunohistochemistry in type 1 mice showed GC loss but no difference in pericyte density or acellular capillaries. The results suggest that RDN may precede the established clinical and morphometric vascular changes caused by DM and represent a paradigm shift in our understanding of ocular diabetic complications.

INTRAVITREAL VERSUS SUBRETINAL ADMINISTRATION OF RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR COMBINED WITH GAS FOR ACUTE SUBMACULAR HEMORRHAGES DUE TO AGE-RELATED MACULAR DEGENERATION: An Exploratory Prospective Study.

PURPOSE: Current management of submacular hemorrhage (SMH) favors vitrectomy and gas with subretinal administration of recombinant tissue plasminogen activator (rtPA) over mere intravitreal rtPA injections and gas. In this study, we aimed to compare the effectiveness of both treatment modalities to displace submacular blood. METHODS: Twenty-four patients with SMH secondary to age-related macular degeneration were included. The SMH had to exist ≤14 days at time of surgery and SMH thickness had to be between 250 µm and 1,250 µm. Patients were randomized to either intravitreal injections of rtPA, perfluoropropane (C3F8) gas, and bevacizumab (n = 12) or vitrectomy with subretinal rtPA administration, intravitreal C3F8 gas, and bevacizumab (n = 12). The SMH volume change was measured on spectral domain optical coherence tomography postoperatively within a 2.5-mm cylinder centered at the fovea. RESULTS: Median relative volume reduction of subretinal blood at 6 weeks postoperatively was 97% (95% confidence interval: 91-99%) in the intravitreal rtPA group and 100% (95-100%) in the subretinal rtPA group and did not differ significantly between groups (P = 0.56). CONCLUSION: Both treatment modalities effectively displaced SMH in this exploratory clinical trial. To more definitely study the noninferiority of intravitreal rtPA with gas to subretinal rtPA, vitrectomy with gas, a larger clinical trial would be necessary.

Phase-Resolved Doppler Optical Coherence Tomographic Features in Retinal Angiomatous Proliferation.

PURPOSE: To study patients diagnosed with retinal angiomatous proliferation (RAP) based on conventional imaging techniques with phase-resolved Doppler optical coherence tomography (OCT) to detect and localize blood flow in RAP lesions; and to compare these findings to conventional imaging, which are mostly invasive and give limited information concerning intra- and transretinal blood flow. DESIGN: Single-center, consecutive observational case series. METHODS: Twelve treatment-naïve patients diagnosed with RAP based on fundus examination, fluorescein angiography, and indocyanine green angiography were included. Median age was 79 years (range 65-90). Patients were imaged with an experimental 1040 nm swept-source phase-resolved Doppler OCT instrument. Abnormal flow was defined as intraretinal neovascularization or retinal choroidal anastomosis. RESULTS: In 11 patients adequate phase-resolved Doppler OCT images were obtained showing abnormal blood flow in the RAP lesion. In 4 patients a retinal choroidal anastomosis was found, 3 patients showed intraretinal neovascularization connected with a pigment epithelial detachment, 2 patients showed only intraretinal neovascularization, and in 2 patients flow was limited to the subretinal or sub-retinal pigment epithelial space. CONCLUSIONS: Phase-resolved Doppler OCT is able to detect and localize abnormal blood flow within RAP lesions. Blood flow was mostly confined to the intraretinal structures with or without a connecting pigment epithelial detachment; in one-third of patients a retinal choroidal anastomosis was detected. The potential of angiography with phase-resolved Doppler OCT to accurately distinguish between normal and pathologic blood flow in addition to structural OCT data without invasive procedures will help to further elucidate both retinal and choroidal vascular pathologies like RAP.

Diagnosis and treatment of uveitis; not restricted to the ophthalmologist.

Uveitis is associated with a wide range of underlying causes. Familiarity with its clinical manifestations, referral indications, and treatment strategies are required for the optimal use of current therapeutic options. Uveitis can be caused by infectious and non-infectious factors, resulting in differing prognoses and treatments. The treatment of chronic, non-infectious uveitis has profoundly changed in the last years due to the advent of biologicals, but also of intraocular therapies. In severe uveitis, treatment of the underlying cause, whether ocular or systemic, is required to prevent severe loss of vision. For these purposes, a multidisciplinary clinical approach is important, which is addressed in this review. Relevance for patients: A broad understanding of the different causes of uveitis and the implementation of disease-tailored, multidisciplinary management of uveitis is expected to improve treatment outcomes for patients with different types of uveitis.

Clinical manifestations of patients with intraocular inflammation and positive QuantiFERON-TB gold in-tube test in a country nonendemic for tuberculosis.

PURPOSE: To evaluate clinical manifestations of patients with uveitis and scleritis of unknown origin and positive QuantiFERON-TB Gold In-Tube test (quantiferon) in a country not endemic for tuberculosis. DESIGN: Multicenter retrospective cohort study. METHODS: Retrospective review of the clinical, laboratory, and imaging data of 77 patients. Main outcome measures consisted of ocular and systemic features as well as results of laboratory examinations. RESULTS: Out of all, 60 of 71 (85%) were living for at least 6 months in tuberculosis-endemic regions. Location of uveitis was variable; posterior uveitis (29/77; 38%) was the most frequent. Two clinical entities were commonly noted: retinal occlusive vasculitis (21/77; 27%) and serpiginoid choroiditis (11/77; 14%). Antituberculosis treatment was completed in 32 patients; 29 of them (91%) achieved complete remission. Mean quantiferon level was 7.5 U/mL; 71% had values above 2 U/mL and 41% above 10 U/mL. We observed no associations between quantiferon levels and clinical and/or imaging features. Previous tuberculosis infection was diagnosed in 5 of 77 patients (6.5%), while hilar/mediastinal lymphadenopathy was found in 25 of 76 patients (33%). Of these, 12 were consistent with the diagnosis of sarcoidosis, 9 were typical for (prior) tuberculosis, and 4 were compatible with both diagnoses. CONCLUSIONS: Ocular features of patients with idiopathic uveitis and positive quantiferon were diverse, but retinal occlusive vasculitis and serpiginoid choroiditis were common. The quantiferon levels were usually highly elevated and 33% of patients exhibited lymphadenopathy, suggesting frequently the diagnosis of sarcoidosis. Ocular inflammation reacted favorably to antituberculosis treatment, although only a small minority had documented (prior) tuberculosis.

[Diagnosis and treatment of uveitis; not restricted to the ophthalmologist]. / Diagnose en behandeling van uveїtis; niet beperkt tot de oogarts.

Visual symptoms due to uveitis involve a wide range of possible causes. Familiarity with its clinical manifestations, referral indications and treatment strategies is required for the optimal use of current therapeutic options. Uveitis can be caused by infectious and non-infectious factors, resulting in differing prognoses and treatments. The treatment of chronic, non-infectious uveitis has profoundly changed in the last years due to the advent of biological therapies. In severe uveitis, treatment of the underlying cause is required for the prevention of the loss of vision; multidisciplinary team collaboration is therefore important.

Age and gender-specific reference values of orbital fat and muscle volumes in Caucasians.

AIM: To provide age and gender-specific reference values for orbital fat and muscle volumes (MV) in Caucasian adults. PATIENTS AND METHODS: Computed tomographic scans of 160 orbits from 52 men and 55 women, aged 20-80 years, not affected by orbital disease were evaluated. Orbital bony cavity volume (OV), fat volume (FV) and MV were calculated by a previously validated method using the software program Mimics. Ratios of FV to OV and of MV to OV were determined. RESULTS: OV, FV and MV were all significantly larger in men than in women (p<0.001), but FV/OV and MV/OV were similar in both sexes. OV and MV did not change with age, but FV increased with advancing age in both women (p<0.001) and men (p<0.001). Linear regression analysis with FV/OV and MV/OV ratios as dependent variables and age and gender as independent variables showed a significant correlation between age and FV/OV (r=0.52, p<0.0001) and age and MV/OV (r=-0.26, p=0.001). CONCLUSIONS: Advancing age is associated with an increase of FV/OV and a minor decrease of MV/OV. Gender-specific differences in orbital FV and MV disappear once FV and MV are related to OV, by calculating the ratios FV/OV and MV/OV. Age-specific gender-neutral reference ranges (2.5 and 97.5 percentiles) of FV/OV and MV/OV are presented.

Decreased retinal ganglion cell layer thickness in patients with type 1 diabetes.

PURPOSE. To determine which retinal layers are most affected by diabetes and contribute to thinning of the inner retina and to investigate the relationship between retinal layer thickness (LT) and diabetes duration, diabetic retinopathy (DR) status, age, glycosylated hemoglobin (HbA1c), and the sex of the individual, in patients with type 1 diabetes who have no or minimal DR. METHODS. Mean LT was calculated for the individual retinal layers after automated segmentation of spectral domain-optical coherence tomography scans of patients with diabetes and compared with that in control subjects. Multiple linear regression analysis was used to determine the relationship between LT and HbA1c, age, sex, diabetes duration, and DR status. RESULTS. In patients with minimal DR, the mean ganglion cell layer (GCL) in the pericentral area was 5.1 mum thinner (95% confidence interval [CI], 1.1-9.1 mum), and in the peripheral macula, the mean retinal nerve fiber layer (RNFL) was 3.7 mum thinner (95% CI, 1.3-6.1 mum) than in the control subjects. There was a significant linear correlation (R = 0.53, P < 0.01) between GCL thickness and diabetes duration in the pooled group of patients. Multiple linear regression analysis (R = 0.62, P < 0.01) showed that DR status was the most important explanatory variable. CONCLUSIONS. This study demonstrates GCL thinning in the pericentral area and corresponding loss of RNFL thickness in the peripheral macula in patients with type 1 diabetes and no or minimal DR compared with control subjects. These results support the concept that diabetes has an early neurodegenerative effect on the retina, which occurs even though the vascular component of DR is minimal.