Peripheral Microvascular Abnormalities Associated with Open-Angle Glaucoma.

PURPOSE: To investigate peripheral microvascular abnormalities associated with patients with open-angle glaucoma (OAG). DESIGN: This was a cross-sectional study. PARTICIPANTS: Patients with OAG and controls. METHODS: All subjects underwent detailed ophthalmic evaluation, including Humphrey visual field (HVF) tests and swept source OCT. To evaluate peripheral microvascular abnormalities, nailfold capillaroscopy (NFC) and laser Doppler imaging (LDI) were performed. The presence of microhemorrhages, tortuous capillaries, dilated capillaries, avascular areas, and the capillary density, among other characteristics, were recorded using NFC; fingertip blood flow (FBF) was measured using LDI at different time points, before and 1, 10, and 20 minutes after exposure to a cold stimulus. In addition, venous blood samples were collected to measure serum endothelin-1 (ET-1) concentrations as well as serum autoantibodies. MAIN OUTCOME MEASURES: Presence of microhemorrhages, tortuous capillaries, and dilated capillaries; FBF; ET-1; and autoantibodies. RESULTS: Sixty-eight subjects (43 patients with OAG and 25 controls) were enrolled in the study. Microhemorrhages were found in the nail bed of 65.1% of the patients with OAG compared with 25.0% of the controls (P = 0.003). There was a significant difference in the mean FBF at the baseline in patients with OAG versus controls (293.6 ± 100.2 vs 388.8 ± 52.0 perfusion units, respectively, P < 0.001), together with a significant decrease in the mean FBF 10 and 20 minutes after cold stimulus in patients with OAG in comparison to controls (P < 0.001 for all comparisons). There was a positive correlation between mean baseline FBF and HVF mean deviation (r = 0.27, P = 0.03) and between mean baseline FBF and average retinal nerve fiber layer thickness (r = 0.44, P = 0.001). Neither the analysis of ET-1 concentrations (P= 0.71) nor the autoantibodies measurements (P > 0.05, for all) showed any difference between the 2 groups. CONCLUSIONS: Significant peripheral microvascular abnormalities were found in patients with OAG compared to controls, suggesting that microvascular changes might play a role in the pathogenesis of the disease. In addition, part of these peripheral microvascular abnormalities seems to be correlated with both functional and structural glaucomatous damage. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Structural abnormalities associated with glaucoma using swept-source optical coherence tomography in patients with systemic sclerosis.

PURPOSE: Vasospasm represents an early event in systemic sclerosis (SSc). Ocular vasospasm may induce optic nerve head (ONH) damage and has been involved in the pathogenesis of glaucoma, especially normal-tension glaucoma (NTG). We aimed to investigate the presence of structural abnormalities associated with NTG using swept-source optical coherence tomography (SS-OCT) and to correlate the OCT parameters with clinical, capillaroscopy and digital blood flow measures in patients with SSc. METHODS: In this cross-sectional study, 40 patients with SSc and 23 age-matched controls were included. The following parameters were measured using SS-OCT: mean and sectoral retinal nerve fibre layer (RNFL) thickness, macular ganglion cell layer complex (GCC) thickness and ONH morphology. Nailfold capillaroscopy (NFC) and digital blood flow measurements using laser Doppler imaging (LDI) were performed in all subjects. RESULTS: Patients with SSc showed a thinner temporal RNFL than the controls (69.23 ± 11.74 versus 83.35 ± 20.19 µm, p = 0.001). The other parameters were similar between the two groups. In SSc patients, there was an inverse correlation between the disease duration and the average, superior and inferior RNFL thickness and the GCC thickness and between Raynaud's phenomenon duration and the average RNFL and GCC thickness (p < 0.05). NFC and LDI measurements did not show correlations with OCT parameters. CONCLUSION: A thinner temporal RNFL and the correlation between Raynaud's phenomenon and disease duration and structural abnormalities on OCT suggest the presence of early ganglion cell damage in patients with SSc. Although mild, these findings indicate the need to monitor ocular abnormalities in SSc.

Characterization of Prelaminar Wedge-Shaped Defects in Primary Open-Angle Glaucoma.

PURPOSE: To determine the clinical relevance of prelaminar wedge defects (PLWDs) detected by swept-source optical coherence tomography (SS-OCT) in primary open-angle glaucoma (POAG). MATERIALS AND METHODS: In this retrospective case-control study, PLWDs were defined as triangular-shaped defects at the surface of the optic nerve prelaminar tissue, not adjacent to blood vessels, present on cross-sectional SS-OCT scans. Two observers masked to diagnosis independently reviewed scans to detect PLWDs and lamina cribrosa defects. History of disc hemorrhage, occurring within 2 years prior to imaging, was obtained from chart review. One eye per subject was randomly selected. Two-sided t-tests, analysis of variance with Bonferroni correction, and multivariable logistic regression analysis were performed to explore demographic and clinical features associated with PLWDs. RESULTS: 40 POAG and 23 control eyes were included. PLWDS were found in 27.5% of POAG (n = 11) and 4.3% of controls (n = 1, p = .04). Eyes with repeat SS-OCT imaging (7 POAG and 0 controls) had persistent PLWDs. More POAG eyes with PLWDs had a history of disc hemorrhage (45.5%) than POAG eyes without PLWDs (3.4%, p = .004). On multivariable analysis, compared to POAG without PLWDs, POAG with PLWDs had increased odds of observed disc hemorrhage (OR = 21.6, 95% CI, 2.2-589.0, p = .02) after adjusting for age, gender, visual field mean deviation and maximum intraocular pressure (IOP). POAG with PLWDs had more lamina cribrosa defects (45.5%) than POAG without PLWDs (3.4%, p = .01) but did not differ significantly from controls (8.7%, p = .07). Compared to all patients without PLWDs, patients with PLWDs had increased odds of having lamina cribrosa defects (OR = 44.8; 95% CI, 6.3-703.6, p < .001) after adjusting for age, gender, and maximum IOP. CONCLUSIONS: PLWDs were more frequently found in POAG than control eyes and were associated with a history of disc hemorrhage and lamina cribrosa defects. PLWDs may be a useful imaging biomarker of glaucomatous damage.

Angle Anatomy and Glaucoma in Patients With Boston Keratoprosthesis.

PURPOSE: To quantitatively analyze the angle anatomy in eyes with a Boston type 1 keratoprosthesis (KPro) using anterior segment optical coherence tomography (AS-OCT) and to assess the diagnostic ability of AS-OCT in KPro-associated glaucoma. METHODS: AS-OCT (RTVue) images from KPro eyes with and without glaucoma were reviewed. The angle opening distance at 500 µm from the scleral spur (AOD500), trabecular-iris angle at 500 µm from the scleral spur (TIA500), and trabecular-iris surface area at 500 µm from the scleral spur (TISA500) were measured by 2 observers masked to the diagnosis. The measurements for each visible quadrant were compared between KPro eyes with and without glaucoma. RESULTS: Twenty-two eyes with glaucoma and 17 eyes without glaucoma from 39 patients with KPro were included. Of the 4 quadrants imaged, the temporal angle was the most visible (79.5%) and angle measurements of the temporal quadrant were the only ones that differentiated the 2 groups: the mean AOD500, TIA500, and TISA500 were significantly lower in KPro eyes with glaucoma than without glaucoma (388.2 ± 234.4 µm vs. 624.5 ± 310.5 µm, P = 0.02; 26.1 ± 14.0 degrees vs. 39.1 ± 17.1 degrees, P = 0.03; and 0.15 ± 0.09 mm vs. 0.23 ± 0.12 mm, P = 0.03; respectively). The highest area under the receiver operating characteristic curve for detecting glaucoma was 0.75 for temporal TIA500 (95% confidence interval 0.57-0.94, P = 0.02) with 50% specificity at 80% of sensitivity and a cutoff value of 37 degrees. CONCLUSIONS: The temporal angle was the most visible on AS-OCT in eyes with a KPro. Significant narrowing of the temporal angle detected on AS-OCT was associated with glaucoma in these eyes.

Blood Levels of Tumor Necrosis Factor Alpha and Its Type 2 Receptor Are Elevated in Patients with Boston Type I Keratoprosthesis.

Purpose: Boston keratoprosthesis (KPro) patients are prone to glaucoma even with well-controlled intraocular pressure (IOP). Recent experimental data have shown that soluble tumor necrosis factor alpha (TNF-α) after ocular injury may contribute to progressive retinal damage and subsequent glaucoma. This study evaluates the blood plasma levels of soluble TNF-α, TNF receptors 1 (TNFR1) and 2 (TNFR2), and leptin in patients with Boston type I KPro. Methods: Venous blood samples were collected from KPro patients with glaucoma (KPro G, n = 19), KPro patients without glaucoma (KPro NoG, n = 12), primary angle closure glaucoma without KPro (PACG, n = 13), and narrow angles without glaucoma or KPro (NA, n = 21). TNF-α, TNFR1, TNFR2, and leptin levels were quantified using the enzyme-linked immunosorbent assay. Erythrocyte sedimentation rate (ESR) was assessed using the Westergren test. Patients with underlying autoimmune conditions or diabetes were excluded from the study. Results: All groups had similar age, body mass index (BMI), IOP, and ESR (p ≥ 0.11). The mean time from KPro surgery to blood draw was 5.3 ± 3.7 years. Compared to NA patients (0.72 ± 0.3 pg/ml), KPro G and KPro NoG patients had higher blood plasma levels of TNF-α (1.18 ± 0.58 pg/ml, p = 0.006; 1.16 ± 0.50 pg/ml, p = 0.04, respectively). Similarly, KPro G patients had higher blood plasma levels of TNFR2 (2768 ± 1368 pg/ml) than NA patients (2020 ± 435 pg/ml, p = 0.048). In multivariate analysis, KPro status remained positively associated with TNF-α levels (ß = 0.36; 95% confidence intervals [CI]: 0.14-0.58; p = 0.002) and TNFR2 levels (ß = 458.3; 95% CI: 32.8-883.7; p = 0.035) after adjusting for age, gender, BMI, glaucoma status, and ESR. TNFR1 and leptin levels were not significantly different in the study groups. Conclusions: We detected elevated serum levels of TNF-α and TNFR2 in KPro patients. Longitudinal studies are needed to establish TNF-α and TNFR2 as serum biomarkers related to KPro surgery. Abbreviations: BCVA: best corrected visual acuity; BMI: body mass index; CDR: cup-to-disc ratio; EDTA: ethylenediaminetetraacetic acid; ELISA: enzyme-linked immunosorbent assay; ESR: erythrocyte sedimentation rate; HVF: Humphrey visual field; IOP: intraocular pressure; KPro G: keratoprosthesis with glaucoma; KPro NoG: keratoprosthesis without glaucoma; KPro: keratoprosthesis; MD: mean deviation; NA: narrow angle; non-KPro: without keratoprosthesis; PACG: primary angle closure glaucoma; RNFL: retinal nerve fiber layer; TNF-α: tumor necrosis factor alpha; TNFR1: tumor necrosis factor receptor 1; TNFR2: tumor necrosis factor receptor 2.

Thin minimal rim width at Bruch's membrane opening is associated with glaucomatous paracentral visual field loss.

PURPOSE: To compare optic nerve head (ONH) measurements in glaucomatous eyes with paracentral visual field (VF) loss to eyes with peripheral VF loss and controls. METHODS: Open-angle glaucoma (OAG) patients with early paracentral VF loss or isolated peripheral VF loss as well as control subjects underwent ONH imaging with swept-source optical coherence tomography (OCT) and retinal nerve fiber layer (RNFL) imaging with spectral-domain OCT. Minimum rim width at Bruch's membrane opening (BMO-MRW), lamina cribrosa depth (LCD), and RNFL thickness were compared among the glaucoma and control groups with one-way analysis of variance, Kruskal-Wallis test, and multiple regression analysis. RESULTS: Twenty-nine eyes from 29 OAG patients (15 early paracentral and 14 isolated peripheral VF loss) and 20 eyes of 20 control subjects were included. The early paracentral and isolated peripheral VF loss groups had similar VF mean deviation (MD) (-5.3±2.7 dB and -3.7±3.0 dB, p=0.15, respectively). Global BMO-MRW was lower in OAG eyes than in controls (193.8±40.0 vs 322.7±62.2 µm, p<0.001), but similar between eyes with early paracentral VF loss and those with isolated peripheral VF loss (187.6±43.4 vs 200.6±36.3 µm; p>0.99). In contrast, the minimal BMO-MRW was lower in eyes with early paracentral loss (69.0±33.6 µm) than in eyes with isolated peripheral loss (107.7±40.2 µm; p=0.03) or control eyes (200.1±40.8 µm; p<0.001). Average and thinnest RNFL thickness did not differ between OAG groups (p=0.61 and 0.19, respectively). Horizontal and vertical LCD did not differ among the OAG groups and controls (p=0.80 and 0.82, respectively). Multivariable linear regression analysis among OAG cases confirmed the association between lower minimal BMO-MRW and early paracentral VF loss (ß=-38.3 µm; 95% confidence interval, -69.8 to -6.8 µm; p=0.02) after adjusting for age, gender, MD, and disc size. CONCLUSION: Thin minimal BMO-MRW may represent a new structural biomarker associated with early glaucomatous paracentral VF loss.

Optic Nerve Head Characteristics in Chronic Angle Closure Glaucoma Detected by Swept-Source OCT.

PURPOSE: To compare structural features in prelaminar and laminar tissues of the optic nerve head (ONH) in chronic angle closure glaucoma (CACG), primary open angle glaucoma (POAG), and control subjects. MATERIALS AND METHODS: ONH imaging was performed using swept-source optical coherence tomography (SS-OCT) for measurements of minimum rim width at Bruch's membrane opening (BMO-MRW), horizontal, and vertical lamina cribrosa depth (LCD). Prelaminar defects, categorized as hole and wedge, and lamina cribrosa (LC) defects were identified. Enhanced depth imaging spectral domain OCT (EDI-OCT) customized to perform high-resolution volume scans was used in conjunction to further characterize prelaminar holes. One eye per subject was analyzed. RESULTS: Eighty subjects (20 CACG, 40 POAG, and 20 controls) were included in the study. CACG and POAG groups had similar mean deviation on Humphrey visual field testing (-6.9 ± 5.1 vs. -6.3 ± 6.0 dB, p > 0.05) and IOP on the day of imaging (14.0 ± 3.1 vs. 13.8 ± 2.7 mmHg, p > 0.05). Thinnest and global BMO-MRW in CACG (120.3 ± 44.8, 225.5 ± 53.9 µm) and POAG (109.7 ± 56.3, 213.8 ± 59.7 µm) groups were lower than controls (200.1 ± 40.8, 308.3 ± 70.8 µm; p < 0.001 for both). Prelaminar holes were most frequent in CACG (65.0%) than POAG (25.0%, p=0.008) or control groups (20.0%, p=0.01). After adjusting for demographic and ophthalmic covariates, CACG was associated with increased odds of having prelaminar holes compared to POAG (odds ratio, 9.79; 95% CI, 2.12-45.19; p=0.003). Hole volume was similar between CACG and POAG (p > 0.05), but the CACG group had more holes per scan than POAG (maximum 2.5 ± 1.9 vs. 1.2 ± 0.4, p=0.02). Prelaminar wedge defects were less common in the CACG than the POAG group (5.0% vs. 37.5%, p=0.02). The CACG group did not differ from controls in laminar characteristics, such as LCD and LC defects. CONCLUSIONS: SS-OCT evaluation of the ONH revealed more frequent prelaminar holes in CACG compared to POAG and control patients.

The Role of the Back Plate in Angle Anatomy with the Boston Type I Keratoprosthesis.

PURPOSE: To quantitatively evaluate the angle anatomy in eyes with the Boston type I keratoprosthesis (B-KPro) differing in the back plate (BP) material and size using anterior segment optical coherence tomography. METHODS: B-KPro eyes with poly(methyl methacrylate) (PMMA) (7.0 and 8.5 mm) and titanium (7.0, 8.5, and 9.5 mm) BPs were imaged with anterior segment optical coherence tomography. The angle opening distance at 500 µm from the scleral spur (AOD500), trabecular iris surface area at 500 µm from the scleral spur (TISA500), and trabecular iris angle at 500 µm from the scleral spur (TIA500) were measured. Among the visible quadrants, the average, the temporal, the widest, and the narrowest angle of each eye were included in the analysis. Average time between B-KPro implantation and imaging was 7.5 ± 1.4 years for a PMMA BP and 2.4 ± 2.3 years for a titanium BP (P < 0.0001). RESULTS: We analyzed 17 B-KPro eyes with PMMA BPs and 24 B-KPro eyes with titanium BPs. The average AOD500 (394.1 ± 226.9 vs. 454.5 ± 255.6 µm, P = 0.44), average TIA500 (26.2 ± 14.2 vs. 29.8 ± 13.9 degrees, P = 0.43), and average TISA500 (0.15 ± 0.08 vs. 0.17 ± 0.10 µm, P = 0.52) were not statistically different between eyes with PMMA and titanium BPs, nor were the temporal, the narrowest, and the widest angle measurements of each eye (all P > 0.05). Similarly, no significant differences were found between the angle measurements of B-KPro eyes with a titanium BP diameter of 8.5 or 9.5 mm (all P > 0.05). CONCLUSIONS: We successfully visualized the angle anatomy in 66.1% of the imaged eyes, including all BPs studied. Neither the material nor the size of the B-KPro BP had a significant impact on the angle anatomy.

Comparison of swept-source and enhanced depth imaging spectral-domain optical coherence tomography in quantitative characterisation of the optic nerve head.

AIMS: To compare swept-source optical coherence tomography (SS-OCT) and enhanced depth imaging spectral-domain OCT (EDI-OCT) in quantitative assessment of optic nerve head (ONH) parameters. METHODS: In a cross-sectional study, patients with primary open angle glaucoma (POAG) and age-matched control subjects underwent SS-OCT and EDI-OCT B-scans of the ONH in a single visit. Two masked readers independently measured the horizontal and vertical lamina cribrosa depth (LCDH and LCDV, respectively), as well as thinnest Bruch's membrane opening minimum rim width (BMO-MRW) from SS-OCT and EDI-OCT scans. We assessed agreement between SS-OCT and EDI-OCT measurements by linear regression models, Bland-Altman analysis and concordance correlation coefficients (CCC). Intrareader and inter-reader reproducibility was assessed using intraclass correlation coefficients (ICC). RESULTS: One eye from each of 40 patients with POAG and 20 controls were included. All three ONH measurements were higher on SS-OCT than on EDI-OCT, with significant differences in LCDH (mean difference=31.7 µm, p<0.01) and thinnest BMO-MRW (mean difference=20.5 µm, p<0.01). Linear regression models described the agreement between SS-OCT and EDI-OCT measurements with R2>0.8 for LCDH among both patients with POAG and controls and for thinnest BMO-MRW among patients with POAG. The CCC was >0.8 overall for each parameter. Intrareader and inter-reader ICCs were ≥0.989 and ≥0.964, respectively, for all parameters. CONCLUSIONS: LCDH, LCDV and thinnest BMO-MRW measurements are not interchangeable between SS-OCT and EDI-OCT, but show good intrareader and inter-reader reproducibility and interdevice agreement for quantitative characterisation of the ONH, particularly among patients with glaucoma.

The evolution of corneal and refractive surgery with the femtosecond laser.

The use of femtosecond lasers has created an evolution in modern corneal and refractive surgery. With accuracy, safety, and repeatability, eye surgeons can utilize the femtosecond laser in almost all anterior refractive procedures; laser in situ keratomileusis (LASIK), small incision lenticule extraction (SMILE), penetrating keratoplasty (PKP), insertion of intracorneal ring segments, anterior and posterior lamellar keratoplasty (Deep anterior lamellar keratoplasty (DALK) and Descemet's stripping endothelial keratoplasty (DSEK)), insertion of corneal inlays and cataract surgery. As the technology matures, it will push surgical limits and open new avenues for ophthalmic intervention in areas not yet explored. As we witness the transition from femto-LASIK to femto-cataract surgery it becomes obvious that this innovation is here to stay. This article presents some of the most relevant advances of femtosecond lasers to modern corneal and refractive surgery.

Periprosthetic Tissue Loss in Patients With Idiopathic Vitreous Inflammation After the Boston Keratoprosthesis.

PURPOSE: Idiopathic vitritis is a poorly understood complication after Boston keratoprosthesis surgery with unclear etiology. We sought to determine whether an association exists between periprosthetic corneal tissue loss and the development of idiopathic vitritis in keratoprosthesis recipients. METHODS: Thirteen Boston type I keratoprosthesis recipient eyes with a history of idiopathic vitritis and 34 type I keratoprosthesis recipient eyes with no history of idiopathic vitritis underwent anterior segment optical coherence tomography (AS-OCT) at a median time postoperatively of 2.4 years versus 1.9 years (range, 0.5-14.2 vs. 0.1-13.6 years), respectively. Areas of corneal graft tissue loss ("gaps") around the keratoprosthesis stem were identified and analyzed by 2 masked observers. The difference in the presence, number, and size of gaps was compared between cases and controls. RESULTS: A periprosthetic gap was identified more commonly in idiopathic vitritis cases than in controls on AS-OCT (11/13, 86% vs. 11/34, 33.3%, P < 0.001). The number of gaps between cases and controls was also significantly different (2.6 ± 1.6 vs. 0.5 ± 0.8, P < 0.001), but not the estimated gap area (0.056 ± 0.049 mm² vs. 0.039 ± 0.025 mm², P = 0.22). CONCLUSIONS: A significantly higher proportion of keratoprosthesis recipient eyes with idiopathic vitritis had corneal tissue loss around the keratoprosthesis stem than did controls. Tissue loss could serve as an entry point for debris or bacterial components, triggering idiopathic vitritis. Our study underscores the utility of AS-OCT imaging in the postoperative management of keratoprosthesis patients.

Clinicians' perspectives on the use of drug-eluting contact lenses for the treatment of glaucoma.

Glaucoma is the leading cause of irreversible blindness worldwide. The perspective of clinicians who treat the disease is important and may ultimately dictate the adoption of new treatment modalities, such as drug-eluting contact lenses. Recent advances have enabled contact lenses to serve as a sustained-release drug-delivery platform capable of treating glaucoma. This review covers the medical treatment of glaucoma, suboptimal adherence rates to treatment, and factors that may influence the clinical applicability of drug-eluting contact lenses. Ophthalmologists who treat glaucoma were surveyed to determine their perspective on treatment adherence, bandage contact lens use and the use of a drug-eluting contact lens to treat glaucoma. Given the challenge of treating glaucoma and the clinical need for improved drug delivery, drug-eluting contact lenses appear to be a promising treatment option.