Francesco Oddone

Corneal biomechanical characteristics in patients with diabetes mellitus

PURPOSE: To compare the corneal biomechanical properties in eyes of patients with diabetes mellitus and in those of subjects without diabetes mellitus. SETTING: Hospital eye clinic. DESIGN: Comparative case series. METHODS: Corneal hysteresis (CH) and corneal response factor (CRF) were measured in diabetic patients and nondiabetic subjects using the Ocular Response Analyzer. Central corneal thickness (CCT) and intraocular pressure (IOP) were also measured. Differences in corneal biomechanical properties were determined using a 1‐way analysis of variance. Interassociations between ocular and diabetic parameters were also evaluated. RESULTS: Sixty‐one eyes of 61 diabetic patients and 123 eyes of 123 nondiabetic subjects were evaluated. The CRF was significantly greater in the eyes of diabetic patients (mean difference, 1.09 mm Hg; 95% confidence interval [CI], 0.49‐1.69; P = .001). There were no significant differences in CCT or CH between groups (CH: mean difference, 0.38 mm Hg; 95% CI, −0.21 to 0.97 mm Hg; P = .21; CCT: mean difference, 0.13 μm; 95% CI, −10.6 to 10.8 μm; P =.98). Corneal hysteresis and CRF were weakly correlated with blood glucose concentration (slopes: CH: 0.28; 95% CI, 0.03–0.50; P = .03; CRF: 0.27; 95% CI 0.02‐0.49; P = .04). In a multiple regression analysis, the effects of blood glucose concentration were reduced and age and CCT became significant predictors of CH and CRF. CONCLUSIONS: The eyes in diabetic patients displayed altered corneal biomechanics that may be related to blood glucose concentration. Further studies are required to establish the effects of long‐term poor glucose control on corneal biomechanical properties and how this might affect the diabetic patient’s response to refractive surgery procedures. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Influence of Disc Size on Optic Nerve Head versus Retinal Nerve Fiber Layer Assessment for Diagnosing Glaucoma

PURPOSE To explore and compare the influence of optic disc size on the diagnostic accuracy of retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) quantitative assessment. DESIGN Observational, cross-sectional evaluation of diagnostic tests. PARTICIPANTS We included 120 eyes from 50 normal subjects and 70 glaucomatous patients classified by the presence of a repeatable visual field defect for the analysis. TESTING The RNFL thickness was measured by scanning laser polarimetry with variable corneal compensator (GDx-VCC, Carl-Zeiss Meditec, Dublin, CA) and spectral-domain optical coherence tomography (Cirrus HD-OCT, Carl Zeiss Meditec, Inc). We obtained ONH imaging by means of confocal scanning laser ophthalmoscopy (HRT3; Heidelberg Engineering, GmbH, Dossenheim, Germany). MAIN OUTCOME MEASURES Sensitivity and specificity for normative classifications, sensitivity at fixed specificity and area under the receiver operating characteristics curve (AUC) for continuous parameters. A logistic marginal regression model and coefficients of variation (CoV) have been used to test and quantify the influence of optic disc size on the diagnostic accuracy of the 3 technologies under investigation. RESULTS Among continuous parameters average RNFL thickness for Cirrus HD-OCT, nerve fiber indicator for GDx-VCC and cup shape measure for the HRT3 showed the best diagnostic accuracy with an AUC of 0.97, 0.94, and 0.94, respectively. Among normative classifications, the highest sensitivity and specificity were found for OCT average RNFL thickness (75.8% and 94.7%), for GDx superior thickness (77.1% and 97.5%), for HRT3 Moorfields regression analysis result (89.4% and 73.7%) and for HRT3 GPS global (92.3% and 76.5%). The diagnostic performance of HRT3 parameters seemed to be significantly influenced by optic disc size, although the same was not true for Cirrus HD-OCT and GDx VCC. The most steady performers for each imaging device across disc size groups were Cirrus HD-OCT average thickness (CoV, 1.6%), GDx-VCC inferior thickness (CoV, 2.5%), and HRT3 GPS temporal and nasal (CoV, 21.4%). CONCLUSIONS The diagnostic accuracy of quantitative RNFL assessment as performed by Cirrus HD-OCT and GDx-VCC is high and virtually unaffected or only minimally affected by the size of the optic disc and may provide more consistent diagnostic outcomes across small and large discs than ONH assessment as performed by HRT3.

Retinal functional changes measured by microperimetry in neovascular age-related macular degeneration treated with ranibizumab: 24-month results.

Purpose: The purpose of this study was to assess long-term functional and structural retinal changes in patients with neovascular age-related macular degeneration treated with intravitreal 0.5 mg ranibizumab. Methods: Eighteen patients with neovascular age-related macular degeneration have been evaluated in this retrospective 24-month follow-up study. All patients have been treated with 3 injections of 0.5 mg ranibizumab 1 month apart and retreated according to predefined criteria. At baseline, all patients were subjected to visual acuity, fluorescein angiography, MP1 microperimetry, and Stratus optical coherence tomography. Although visual acuity and optical coherence tomography were repeated 28 ± 2 days after each injection, MP1 was performed at 6, 12, and 24 months. Results: Seventeen of 18 and 14 of 18 patients completed 12 and 24 months of follow-up, respectively. Mean retinal sensitivity significantly improved from 3.89 ± 3.0 dB to 7.33 ± 4.11 dB at 24 months (P = 0.024). Mean visual acuity improved from 48.67 ± 8.59 to 59.17 ± 16.45 at 24 months (P = 0.049). Visual acuity improved to ≥15 letters in 33.3% (6 of 18) of patients and <15 letters in 44.4% (8 of 18); 22.2% (4 of 18) of patients lost <15 letters at 24 months. Five of 13 patients (38.5%) with either an instable or relatively instable fixation at baseline showed improvement of fixation stability at 24 months. Central retinal thickness significantly decreased from 310.5 ± 85.7 to 232.9 ± 60.1 at 24 months (P = 0.0001). Conclusion: Intravitreal injections of 0.5 mg ranibizumab determine progressive improvement of retinal sensitivity until 24 months, although visual acuity levels off after 6 months, suggesting that microperimetry may give additional information about macular function not given by visual acuity alone.

The role of Humphrey Matrix testing in the early diagnosis of retinopathy in type 1 diabetes

Aim: The aim of the study was to investigate the role of Humphrey Matrix threshold testing in the detection of early functional retinal impairment in subjects with type 1 diabetes mellitus (DM1) without any signs of retinal vasculopathy, and to investigate the relationship between both functional and structural retinal parameters and metabolic control. Methods: Thirty eyes of 30 subjects with DM1, with no sign of retinal vasculopathy, and 30 eyes of 30 age- and sex-matched healthy subjects were enrolled in this cross-sectional clinical study. Functional testing included Humphrey Matrix perimetry and white-on-white Humphrey visual field perimetry (HFA), while retinal nerve fibre layer (RNFL) thickness was measured by scanning laser polarimetry with variable corneal birefringence compensator (GDx VCC). Results: Matrix mean deviation (MD) was found to be significantly reduced in subjects with DM1 compared with controls (−1.10 (SD 2.98; 95% CI −2.21 to 0.01) vs 1.37 (SD 2.11; 95% CI 0.58 to 2.16), p = 0.0005). HFA MD and pattern standard deviation (PSD) were significantly worse in subjects with DM1 compared with controls (p = 0.010 and p = 0.013 respectively). Among structural parameters, average peripapillary RNFL thickness was reduced in DM1 subjects (p = 0.006). Matrix MD and HFA MD and PSD, and average peripapillary and superior RNFL, were significantly reduced in subjects with DM1 with HbA1c ⩾7% compared with controls. Conclusions: Functional and structural retinal testing by Humphrey Matrix and GDx VCC could be useful for the identification of early retinal impairment in people with DM1 with no sign of retinal vasculopathy.

Reproducibility of Macular Thickness Measurements Using Cirrus SD-OCT in Neovascular Age-Related Macular Degeneration

PURPOSE To assess the test-retest variability of central and sectorial macular thickness measurements obtained by Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) in neovascular age-related macular degeneration (nAMD). METHODS Macular thickness measurements of nine standard ETDRS subfields were obtained and analyzed. The repeatability of macular thickness measurements by Cirrus HD-OCT was assessed by examining the intrasession within subject standard deviation (Sw), coefficient of repeatability (CR), and coefficient of variation (CV), before and after eyes with retinal segmentation errors were excluded. RESULTS Forty-nine nAMD eyes of 49 consecutive patients were included in the study. The CR for the central macular subfield was 42.4 microm (10.5%) and ranged from 12.1 microm (3.7%) for the outer nasal to 41.8 microm (11.4%) for the inner nasal subfields. In a secondary analysis, eyes affected by erroneous detection of inner and outer retinal boundaries (6/49, 12.24%) were excluded. The revised coefficient of repeatability for the central macular subfield was 26.1 microm (8.1%) and ranged from 10.3 microm (3.8%) for the outer superior to 30.2 microm (8.3%) for the inner nasal subfields. CONCLUSIONS Overall, the test-retest variability of Cirrus HD-OCT is good for the central and sectorial macular subfields, with a low incidence of scan artifacts.

Efficacy of the fixed combinations of bimatoprost or latanoprost plus timolol in patients uncontrolled with prostaglandin monotherapy: A multicenter, randomized, investigator-masked, clinical study

Purpose To compare the efficacy and tolerability of a once-daily evening dose of bimatoprost/timolol fixed combination (BTFC) with that of a once-daily evening dose of latanoprost/timolol fixed combination (LTFC) in patients not controlled with prostaglandins analogues monotherapy. Methods A total of 82 patients on prostaglandin analogues monotherapy were enrolled in this prospective, multicenter, investigator masked, clinical study and were randomized to either BTFC (n=47) or LTFC (n=35) topical therapy once at night for 12 weeks. The primary endpoint of the study was to compare the mean daily intraocular pressure (IOP) reduction from baseline between the two treatment arms. Secondary endpoints included the mean daily IOP at 1 and 3 months compared to baseline and the percentage of patients showing a mean IOP reduction from baseline greater than or equal to 15% or 20%. Results Mean IOP at baseline was 22.7±2.0 and 22.1±2.6 mmHg in the BTFC and LTFC groups, respectively (p=0.23). Both treatments were effective in reducing the IOP from baseline. The mean IOP reduction was significantly greater in the BTFC group than in the LTFC group (–21.4% vs −13.7%, p<0.001). A higher percentage of patients in the BTFC group showed a mean IOP reduction from baseline ≥ 15% (72.3% vs 40.0%) and ≥ 20% (61.7% vs 17.1%) compared to patients in the LTFC group. Conclusions Both BTFC and LTFC were more effective versus the monotherapy with prostaglandin analogues. BTFC demonstrated higher performance than LTFC in terms of relative IOP reduction.

Retinal functional changes measured by microperimetry in neovascular age-related macular degeneration patients treated with ranibizumab.

Purpose: To assess functional and structural retinal changes in patients with neovascular age-related macular degeneration treated with intravitreal ranibizumab 0.5 mg. Methods: Eighteen patients with neovascular age-related macular degeneration have been evaluated in this retrospective 24-week follow-up study. All patients were treated with three injections of ranibizumab 0.5 mg, 1 month apart and retreated according to predefined criteria. At baseline, all patients were subjected to visual acuity measurement, fluorescein angiography, microperimetry, and optical coherence tomography stratus. Visual acuity, microperimetry, and optical coherence tomography evaluations were repeated 28 ± 2 days after each injection. Results: Mean retinal sensitivity significantly improved from 3.89 ± 3.0 dB at baseline to 6.61 ± 3.4 dB at 24 weeks (P = 0.044). Mean visual acuity significantly improved from 48.67 ± 8.58 to 60.72 ± 16.09 (P = 0.026); visual acuity improved in 44.4% of patients ≥15 letters (24.5 ± 8.0 letters), and in 38.9% of patients improved <15 letters (6.14 ± 3.7 letters); 16.7% of patients lost <15 letters (7.3 ± 2.1 letters). An improvement of fixation stability from baseline was observed in 33.3% of patients. Central macular thickness significantly decreased from 310.5 ± 85.7 &mgr;m to 217.3 ± 46.8 &mgr;m at 24 weeks (P < 0.001). Conclusions: Although visual acuity and retinal thickness changes seemed to be almost maximum at 4 weeks after intravitreal ranibizumab 0.5 mg, retinal sensitivity as measured by microperimetry showed a trend of progressive improvement till 24 weeks suggesting that microperimetry may give additional information about macular function not given by visual acuity alone.

Sector-Based Analysis with the Heidelberg Retinal Tomograph 3 Across Disc Sizes and Glaucoma Stages: A Multicenter Study

PURPOSE To investigate the ability of sectorial analysis using the Heidelberg Retinal Tomograph 3 (HRT3) to discriminate between healthy and glaucomatous eyes and to determine whether this is affected by disc size and glaucoma severity. DESIGN Multicenter, cross-sectional evaluation of diagnostic tests. PARTICIPANTS Two hundred thirty-three eyes from 137 normal subjects and 96 glaucoma patients classified by the presence of a repeatable visual field defect. TESTING Participants underwent imaging with the HRT3, and the diagnostic accuracy of stereometric parameters, Moorfields regression analysis (MRA), and glaucoma probability score (GPS) were analyzed sectorially by glaucoma stage and optic disc size. MAIN OUTCOME MEASURES Sensitivity, specificity, positive and negative predictive values, and the area under the receiver operating characteristics curve (AUC). RESULTS Of stereometric parameters, the cup-to-disc area ratio of the inferotemporal sector had the largest AUC (AUC, 0.74). Both MRA and GPS algorithms showed the best diagnostic accuracy in the inferotemporal sector, with a sensitivity and specificity of 63% and 88% for MRA and 80% and 62% for GPS, respectively. In small discs, sectorial MRA analysis had higher diagnostic accuracy than the global optic nerve head (ONH) analysis (sensitivity of 70% and specificity of 82% in the inferonasal sector), and these findings were confirmed in very large discs (sensitivity of 74% and specificity of 85% in the inferotemporal sector). Similarly, stereometric parameters discriminated better sectorially rather than globally, with different parameters giving the best results in different optic disc size subgroups. MRA sensitivity was weak in the early-glaucoma stage, with slightly higher figures if considered sectorially rather than globally. GPS diagnostic accuracy was very consistent across ONH sectors in each disc size and glaucoma stage subgroup, with no single sector demonstrating better diagnostic accuracy than the global analysis. CONCLUSIONS Heidelberg Retinal Tomograph 3 sectorial analysis showed moderate diagnostic performance and may offer potential advantages over global analysis in the clinical diagnostic process. Small discs are classified more accurately by examining the inferonasal sector, whereas larger discs are classified more accurately by examining the inferotemporal sector. Neither HRT parameters nor classification algorithms seem to be good at the earlier stage of the disease. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Comparison of Travoprost and Bimatoprost plus Timolol Fixed Combinations in Open-Angle Glaucoma Patients Previously Treated with Latanoprost plus Timolol Fixed Combination

PURPOSE To compare the ocular hypotensive effect of bimatoprost plus timolol and travoprost plus timolol fixed combinations in glaucoma patients whose disease was controlled but had not reached their target intraocular pressure (IOP) with the fixed combination of latanoprost plus timolol. DESIGN A 2 × 3-month, multicenter, prospective, randomized, double-masked, cross-over clinical trial. METHODS Eighty-nine open-angle glaucoma (OAG) patients were included. After a 6-week run-in period with latanoprost plus timolol, patients were randomized to either travoprost plus timolol or bimatoprost plus timolol for 3 months. Patients then switched to the opposite therapy for 3 additional months. The primary end point was the comparison of mean daily IOP after 3 months of each treatment. RESULTS At baseline, mean IOP was 16.5 mm Hg (95% confidence interval, 16.0 to 17.0 mm Hg) with treatment with latanoprost plus timolol. Both bimatoprost plus timolol and travoprost plus timolol statistically significantly reduced the mean IOP from baseline (P < .0001). Mean IOP at month 3 was statistically significantly lower in the bimatoprost plus timolol group compared with the travoprost plus timolol group (14.7 mm Hg [95% confidence interval, 14.3 to 15.3 mm Hg] vs 15.4 mm Hg [95% confidence interval, 15.0 to 15.9 mm Hg]; P = .0041). IOP was lower during bimatoprost plus timolol treatment at all time points and statistical significance was reached at 8 am, 11 am, and 5 pm, but not at 2 pm and 8 pm. Both treatments showed similar tolerability profile. CONCLUSIONS Bimatoprost plus timolol and travoprost plus timolol can provide additional IOP-lowering effect in patients not fully controlled with latanoprost plus timolol. The observed additional IOP reduction was greater with bimatoprost plus timolol with a similar tolerability profile.

Demographic and clinical factors associated with development of brimonidine tartrate 0.2%-induced ocular allergy.

Purpose:To identify demographic and clinical characteristics associated with the development of brimonidine tartrate 0.2%-induced ocular allergy. Patients and Methods:In this retrospective study, 133 patients affected by primary open-angle, pigmentary, narrow angle, or pseudo-exfoliative glaucoma and treated with brimonidine tartrate 0.2% were divided into two groups: allergic and non allergic to brimonidine tartrate 0.2%. The distribution of demographic (age and sex), local (history of allergic conjunctivitis, previous eye-drop ocular allergy, use of other concurrent topical medications, amount of topical medications previously used, use of contact lenses, and tear film production), and systemic (history of systemic allergies and use of systemic drugs) factors was evaluated by comparing the brimonidine tartrate 0.2% allergic and the non-allergic groups. Results:In this study, 13.5% of patients (18 of 133) developed brimonidine ocular allergy generally within two weeks from the beginning of treatment (mean time 14.8 ± 17.9 days). The brimonidine tartrate 0.2% allergic group showed a significantly higher frequency of history of ocular allergy to eye-drops (P = 0.048) and to topical beta-blockers (P = 0.019) when compared with the brimonidine tartrate 0.2% non-allergic group. Moreover, the allergic group showed a decreased tear film production (P = 0.044). Conclusion:This study showed that history of eye-drop allergies and reduction of tear film production were more frequently associated with the development of brimonidine tartrate 0.2%-induced ocular allergy.