Subtenon triamcinolone as an adjuvant in mitomycin-C-enhanced trabeculectomy in non-inflammatory glaucomas: A randomized clinical trial.

This unicentric randomized clinical trial was designed to compare the surgical outcomes of mitomycin C-enhanced trabeculectomy (MMC-TRAB) with and without subtenon triamcinolone acetonide (TAAC) injection in patients with non-inflammatory glaucomas. This trial is registered at the Brazilian Registry of Clinical Trials (ReBEC) under the register number RBR-53f8nh. Consecutive non-inflammatory glaucoma patients requiring surgical intervention were randomized into two groups. In the control group, eyes underwent standard MMC-TRAB, while in the intervention group, besides the standard MMC-TRAB, these eyes also received a subtenon TAAC injection (4mg) close to the bleb site at the end of the surgery. The main outcomes of the study were surgical success rates, intraocular pressure (IOP) and number of medications at all timepoints. Success was defined as IOP ≤ 15 mmHg and subdivided in complete or qualified according to the need of medication. A total of 75 eyes of 63 different patients were included (intervention group = 39 eyes; control group = 36 eyes). There was no difference between groups at baseline (p>0.11). Multivariable regression analysis indicated that IOP levels were significantly lower in the intervention group at 18 and 24 months of follow-up when number of medications was considered as a covariate (P<0.001). Complete success rates were higher in the intervention group at 06 (90.9% vs 68.7%; p = 0.03), 12 (87.2% vs 66.7%; p = 0.02) and 18 months (87.2% vs 66.7%; p = 0.02). Additionally, although success rates at 24 months were higher in the intervention group (82.0% vs 66.7%; p = 0.09), this difference did not reach statistical significance. Qualified success rates did not significantly differ between groups at all timepoints. In conclusion, this study found significantly lower IOPs levels at 18 and 24 months of follow-up and higher complete success rates until 18 months of follow-up, with the use of subtenon TAAC as an adjuvant to standard MMC-TRABs in non-inflammatory glaucoma patients.

Elucidation of the role of the lamina cribrosa in glaucoma using optical coherence tomography.

Glaucoma is a chronic and progressive optic neuropathy characterized by the death of retinal ganglion cells and corresponding visual field loss. Despite the growing number of studies on the subject, the pathogenesis of the disease remains unclear. Notwithstanding, several studies have shown that the lamina cribrosa (LC) is considered an anatomic site of glaucomatous optic nerve injury, thus having a key role in the pathophysiology of glaucoma development and progression. Different morphological alterations of the LC have been described in vivo in glaucomatous eyes after the evolution of optical coherence tomography (OCT) devices. The most relevant findings were the reduction of laminar thickness, the presence of localized defects, and the posterior LC displacement. These new laminar parameters documented through OCT are not only promising as possible additional tools for glaucoma diagnosis and monitoring, but also as predictors of disease progression. In spite of the advance of technology, however, proper evaluation of the LC is not yet viable in all eyes. We describe OCT-identified LC changes related to the development and progression of glaucoma and provide future directions based on a critical data analysis, focusing on its clinical relevance and applicability.

Clinical Profiles of Glaucomatous Patients With High-tension and Low-tension Optic Disc Hemorrhages: A Comparative Study.

PRCIS: Patients with low-tension optic disc hemorrhages (DHs) are more frequently women, have a diagnosis of normal-tension glaucoma (NTG) diagnosis and greater visual field (VF) loss. Symptoms of vascular dysregulation and Asian race also seem to be more prevalent in this clinical subtype. PURPOSE: Optic DH is an important glaucoma risk factor, and occurs in a wide intraocular pressure (IOP) range. We sought to characterize distinct clinical subtypes of patients with high-tension disc hemorrhage (HTDH) and low-tension disc hemorrhage (LTDH). PATIENTS AND METHODS: In this cross-sectional study, treated glaucomatous patients with DHs from 2 glaucoma services were consecutively enrolled. Disc photographs were evaluated for the presence of DH by 2 glaucoma specialists. After inclusion, patients were classified on HTDH (IOP≥16 mm Hg) and LTDH (IOP<16 mm Hg; median split). Clinical and ocular data from the time of DH detection were compared between groups. RESULTS: One hundred thirty-three DH patients were included (LTDH=66 eyes; HTDH=67 eyes). Patients with LTDH were more often women than those with HTDH (77% vs. 42%; P=0.030). There was also a trend for a higher prevalence of Asian descendants (24% vs. 9%; P=0.058) and symptoms suggestive of vascular dysregulation (34% vs. 14%; P=0.057) in LTDH patients. Eyes with LTDH also had worse VF mean deviation index (P=0.037), higher prevalence of NTG diagnosis (46% vs. 17%; P<0.001), and tended to have thinner central corneas (P=0.066). CONCLUSIONS: Patients developing DHs with treated IOPs in the low teens seem to more frequently fit in a profile represented by women, NTG diagnosis and greater VF loss. The presence of symptoms suggestive of vascular dysregulation and race also seem to differ between these 2 clinical subtypes. A closer optic disc surveillance is recommended for patients with the LTDH subtype, as they may develop DHs despite seemingly well-controlled IOP.

Structure-function relationships in glaucoma using enhanced depth imaging optical coherence tomography-derived parameters: a cross-sectional observational study.

BACKGROUND: To investigate structural and functional correlations in glaucoma patients using enhanced depth imaging spectral-domain optical coherence tomography (EDI OCT)-derived parameters. METHODS: We prospectively enrolled healthy participants and glaucomatous patients with a wide range of disease stages. All participants underwent visual field (VF) testing (SITA - Standard 24-2; Carl Zeiss Meditec, Dublin, CA) and EDI OCT imaging (Spectralis; Heidelberg Engineering Co., Heidelberg, Germany). The following optic nerve head parameters were measured on serial vertical EDI OCT B-scans by two experienced examiners masked to patients clinical data: lamina cribrosa (LC) thickness and area, prelaminar neural tissue thickness and area, anterior LC depth, Bruch's membrane opening (BMO) and average, superior, and inferior BMO-minimum rim width (BMO-MRW). Only good quality images were considered, and whenever both eyes were eligible, one was randomly selected for analysis. Scatter plots were constructed to investigate correlations between each anatomic parameter and patient's VF status (based on VF index [VFI] values). RESULTS: A total of 73 eyes of 73 patients were included. All EDI OCT parameters evaluated differed significantly between glaucomatous and control eyes (P ≤ 0.045). A secondary analysis, in which glaucomatous patients were divided according to VF mean deviation index values into 3 groups (mild [G1; > - 6 dB], moderate [G2; - 6 to - 12 dB] and advanced [G3; <- 12 dB] glaucoma), revealed that average BMO-MRW was the EDI OCT parameter that presented more significant differences between the different stages of glaucoma. Significant structure-function correlations were found between VFI values and prelaminar neural tissue area (R2 = 0.20, P = 0.017), average BMO-MRW (R2 = 0.35, P ≤ 0.001), superior BMO-MRW (R2 = 0.21, P = 0.012), and inferior BMO-MRW (R2 = 0.27, P = 0.002). No significant correlations were found for LC area and anterior LC depth (P ≥ 0.452). CONCLUSIONS: Evaluating the distribution pattern and structure-function correlations of different laminar and prelaminar EDI OCT-derived parameters in glaucomatous patients, we found better results for neural tissue-based indexes (compared to LC-derived parameters). The diagnostic utility of each parameter deserves further investigations.

In vivo analysis of glaucoma-related features within the optic nerve head using enhanced depth imaging optical coherence tomography.

Structural differences between optic nerve head (ONH) parameters in glaucomatous and non-glaucomatous eyes has been documented, however the association between such parameters in patients with different disease stages is yet to be elucidated. We investigated the relationship between different laminar and prelaminar ONH structures using enhanced depth imaging spectral-domain optical coherence tomography (EDI OCT) in a population with and without glaucoma. In this observational case-control study, we prospectively enrolled healthy individuals and glaucomatous patients with different disease stages. All participants underwent EDI OCT imaging (Heidelberg Engineering). Following ONH parameters were measured on serial vertical B-scans by two examiners masked to patient's clinical data: lamina cribrosa (LC) and prelaminar neural tissue (PLNT) thicknesses, Bruch's membrane opening (BMO) and cup depth. Associations between cup depth, and laminar and prelaminar parameters were evaluated controlling for possible confounding factors such as axial length and disc size. Sixty-four eyes of 64 patients were included (30 with glaucoma and 34 controls). Eyes with glaucoma had significantly lower mean LC and PLNT thickness, and greater mean cup depth than controls (p<0.01). There was a significant negative association between PLNT thickness and cup depth in glaucomatous eyes (R2 = 0.158, p = 0.029). In addition, LC thickness correlated significantly with cup depth (R2 = 0.135, p = 0.045). Eyes with thinner LCs presented deeper cups. Overall, cup depth and BMO had the best and LC thickness had the worst intraobserver and interobserver reproducibility grading. In conclusion, significant associations were seen between cup depth, LC and PLNT thickness. Eyes with deeper cups not only had less neural tissue, but also thinner LCs, independent of disc size and axial length. Best reproducibility was found for prelaminar parameters compared to deeper ONH structures.

Selective laser trabeculoplasty for early glaucoma: analysis of success predictors and adjusted laser outcomes based on the untreated fellow eye.

BACKGROUND: To identify success predictors and to study the role of the fellow untreated eye as a co-variable for adjustment of intraocular pressure (IOP) outcomes following selective laser trabeculoplasty (SLT) in early open-angle glaucoma (OAG) patients. METHODS: A case series was carried out. Patients with uncontrolled early OAG or ocular hypertension (inadequate IOP control requiring additional treatment) underwent SLT (one single laser session) performed by the same surgeon in a standardized fashion. The same preoperative medical regimen was maintained during follow-up for all patients. Post-treatment assessments were scheduled at week 1 and months 1, 2, and 3. In order to account for possible influence of IOP fluctuation on laser outcomes, post-laser IOP values of the treated eye of each patient were also analyzed adjusting for IOP changes (between visits variation) of the untreated fellow eye (adjusted analysis). Pre and post-laser IOP values were compared using paired t-test. Factors associated with the magnitude of IOP reduction were investigated using multiple regression analysis. RESULTS: A total of 45 eyes of 45 patients were enrolled. Mean IOP was reduced from 20.8 ± 5.1 to 14.9 ± 2.9 mmHg at month 3 (p < 0.001). Adjusted success rate (defined as IOP reduction ≥ 20%) was 64% and mean percentage of IOP reduction was 23.1 ± 14.3% at last follow-up visit. Considering unadjusted post-laser IOP values, it was found a 20% greater absolute IOP reduction (median [interquartile range] 6 mmHg [4-7] vs 5 mmHg [3-7]; p = 0.04), with a success rate of 76%. Although baseline IOP was significantly associated with both adjusted and unadjusted post-laser IOP reduction, a stronger association was found when unadjusted IOP values were considered (p < 0.001 and R 2 = 0.35; p < 0.001 and R 2 = 0.67, respectively). Age, mean deviation (MD) index, central corneal thickness and type of glaucoma were not significant predictors (p ≥ 0.150). CONCLUSIONS: In this group of patients with early OAG or ocular hypertension, our short-term results confirmed SLT as a safe and effective alternative for IOP reduction. Although better outcomes were found in eyes with higher preoperative IOP, this effect was mitigated when results were adjusted to the fellow untreated eye (to the influence of between visits-IOP fluctuations).

Simultaneous Therapy with Intravitreal Dexamethasone Implant and Bevacizumab for the Treatment of Macular Edema.

To investigate the safety profile and benefits of a short-term simultaneous treatment regimen combining two drugs-an intravitreal implant of dexamethasone with an intravitreal injection of bevacizumab-in patients with macular edema. This was a retrospective, non-randomized, open-label case series study. Patients were treated between April 2014 and July 2015 and were diagnosed with recurrent macular edema secondary to diabetic retinopathy and retinal vein occlusion. They underwent simultaneous treatment with an intravitreal injection of bevacizumab (1.25 mg) and an intravitreal implant of dexamethasone (0.7 mg). Patients were evaluated at baseline and at each subsequent visit with a complete ophthalmological examination and spectral-domain optical coherence tomography (OCT) scans. They were examined 24 hours after the treatment, and then followed up after 30 days and 60 days. Twenty patients (representing 20 eyes) were included in the study. At the time of injection (i.e., baseline), the best-corrected visual acuity (BCVA) was 0.758 ± 0.42 logarithm of the minimum angle of resolution (logMAR). It improved significantly to 0.51 ± 0.33 logMAR at 1 month and to 0.5 ± 0.34 logMAR at 2 months (P ≤ 0.03). The median baseline central macular thickness (CMT) was 542 µm (interquartile range, 466 - 751 µm). The median CMT decreased significantly to 321 µm (interquartile range, 288-381 µm) at 1 month and 310 µm (interquartile range, 286 - 354 µm) at 2 months (P ≤ 0.0002). The mean intraocular pressure (IOP) increased from 14.9 ± 2.29 mmHg (at baseline) to 16.5 ± 2.99 mmHg (P = 0.04) after 2 months. Two (10%) eyes showed cataract progression. There were no other ocular or systemic complications for the duration of this study. Simultaneous therapy combining a dexamethasone implant plus bevacizumab for macular edema may be an attractive treatment regimen with an acceptable safety profile.

Evaluation of the efficacy and safety of a new device for eye drops instillation in patients with glaucoma.

OBJECTIVE: This study evaluated the efficacy and safety of a new device (Eyedrop(®)) designed for eye drop instillation in patients with and without glaucoma. METHODS: This prospective study included consecutive patients with glaucoma and healthy participants. After a complete eye examination and determination of baseline intraocular pressure (IOP), topical hypotensive medication was introduced in both eyes, and the Eyedrop(®) delivery device (a plastic device in which the bottle with eye drops is inserted) was made available to all participants (with video and written instructions) for use in one eye, randomly chosen. In the second phase, all patients were evaluated by an experienced examiner for IOP determination, investigation of possible associated side effects, and ease of instilling eye drops (by a visual analog scale [VAS]; 0-10). RESULTS: Thirty two participants (mean age 42.3±16.2 years) were evaluated. Of these, 44% had glaucoma. There was no significant difference in mean IOP variation when comparing the eye using (-3.9±2.9 mmHg) or not using the device (-3.3±2.6 mmHg; P=0.36). The subjective rating of the facility of drops instillation was significantly higher with the Eyedrop(®) applicator (VAS =7.6±1.6) than without it (VAS =6.2±1.8; P<0.01), with a higher frequency of positive device-related evaluations (VAS score >5) among participants without prior experience with eye drop instillation (78.6% [11/14]) versus those already experienced (66.7% [12/18]). No difference in the frequency of side effects or in the distribution pattern of fluorescein between eyes was observed (P≥0.63). CONCLUSION: Eyedrop(®) received a better subjective response regarding the ease of instillation of hypotensive eye drops compared to traditional instillation, especially in patients with no previous experience with eye drops. Using the device did not result in any loss of hypotensive effect or increase in the frequency of side effects.

Non-pupillary block angle-closure mechanisms: a comprehensive analysis of their prevalence and treatment outcomes / Mecanismos de fechamento angular sem bloqueio pupilar: análise de prevalência e resultados terapêuticos

Purpose: To assess the prevalence and treatment outcomes of angle-closure mechanisms other than pupillary block in a population of Brazilian patients. Methods: A retrospective chart review was conducted to evaluate patients who had undergone laser peripheral iridotomy (LPI) due to occludable angles at a single institution between July 2009 and April 2012. An occludable angle was defined as an eye in which the posterior trabecular meshwork was not visible for ≥180° on dark-room gonioscopy. Key exclusion criteria were any form of secondary glaucoma and the presence of >90° of peripheral anterior synechiae. Collected data were age, race, gender, angle-closure mechanism (based on indentation goniocopy and ultrasound biomicroscopy), intraocular pressure (IOP), number of antiglaucoma medications and subsequent management during follow-up. If both eyes were eligible, the right eye was arbitrarily selected for analysis. Results: A total of 196 eyes of 196 consecutive patients (mean age 58.3 ± 11.6 years) who underwent LPI were included. In most of the patients [86% (169 patients; 133 women and 36 men]), LPI sucessfully opened the angle. Mean IOP was reduced from 18.3 ± 6.4 mmHg to 15.4 ± 4.5 mmHg after LPI (p<0.01). Among the 27 patients with persistent occludable angles, the most common underlying mechanisms were plateau iris (56%) and lens-induced component (34%). Most of these patients (85%) were treated with argon laser peripheral iridoplasty (ALPI); approximately 90% showed non-occludable angles following the laser procedure (mean IOP reduction of 18.9%), with no significant differences between patients with plateau iris and lens-induced components (p=0.34; mean follow-up of 11.4 ± 3.6 months). Conclusion: Our findings suggest that, in this population of Brazilian patients, several eyes with angle closure were not completely treated with LPI. In the present large case series involving middle-age patients, plateau iris was the ...

Objetivo: Reportar a prevalência e os resultados terapêuticos em casos de fechamento angular por outros mecanismos além de bloqueio pupilar em uma população de pacientes brasileiros. Métodos: Realizou-se um estudo retrospectivo para avaliar pacientes apresentando ângulo oclusível submetidos à iridotomia periférica a laser (LPI), em uma única instituição, entre julho/2009 e abril/2012. Ângulo oclusível foi definido pela não observação do trabeculado posterior em mais de 180° à gonioscopia sem identação. Olhos com glaucomas secundários ou >90º de sinéquia anterior periférica foram excluídos. Foram coletados os seguintes dados: idade, raça, sexo, mecanismo de fechamento angular (com base na gonioscopia e biomicroscopia ultrassônica), pressão intraocular (PIO), número de medicações antiglaucomatosas e manejo subsequente durante o seguimento. Sempre que ambos os olhos eram elegíveis, o olho direito foi escolhido arbitrariamente para análise. Resultados: Foram incluídos 196 olhos de 196 pacientes (58,3 ± 11,6 anos) que foram submetidos à LPI. Na maioria dos casos [86% (169 pacientes; 133 mulheres e 36 homens), a LPI foi capaz de abrir o ângulo. A PIO média foi reduzida de 18,3 ± 6,4 para 15,4 ± 4,5 mmHg após a LPI (p<0,01). Entre os 27 casos que persistiram com ângulo oclusível, os mecanismos mais comuns envolvidos foram íris em platô (56%) e induzido por componente cristaliniano (34%). A maioria desses casos (85%) foram tratados com iridoplastia periférica a laser (ALPI). Aproximadamente 90% tornaram-se não oclusíveis após a ALPI (redução média da PIO de 18,9%), não havendo diferença significativa entre os pacientes com componentes de íris em platô ou cristaliniano (p=0,34; seguimento médio de 11,4 ± 3,6 meses). Conclusões: Nossos resultados sugerem que, nessa população de pacientes brasileiros, parte dos olhos com fechamento angular não foi completamente tratada com LPI. Nesta série de pacientes de meia-idade, a presença de íris em ...

Analysis of neuroretinal rim distribution and vascular pattern in eyes with presumed large physiological cupping: a comparative study.

BACKGROUND: To investigate possible differences in neuroretinal rim distribution, vascular pattern, and peripapillary region appearance between eyes with presumed large physiological optic disc cupping (pLPC) and eyes with minimal optic disc excavation. METHODS: We prospectively enrolled consecutive subjects with pLPC and individuals with minimal excavation (optic disc excavation within normal limits; control group). All eyes had normal visual fields and untreated intraocular pressure (IOP) <21 mmHg. Eyes with pLPC required vertical cup-to-disc ratio (VCDR) ≥ 0.6 and ≥ 30 months of follow-up with no evidence of glaucomatous neuropathy. For controls, VCDR was limited to ≤ 0.5. We compared ocular signs and characteristics related to the neuroretinal rim distribution, vascular pattern, peripapillary region appearance and disc size between groups. Whenever both eyes were eligible, one was randomly selected for analysis. RESULTS: A total of 74 patients (mean age, 45.6 ± 14.9 years) with pLPC and 45 controls (mean age, 44.8 ± 11.6 years) were enrolled (p = 0.76). Median disc size and VCDR was significantly larger in eyes with pLPC compared to controls (p < 0.01). The proportion of eyes with violation of the ISNT rule, laminar dot sign, nasal shifting of the central vessels, nasal excavation and baring of circumlinear vessel was significantly greater in the eyes with pLPC compared to controls (p < 0.01). There were no significant differences regarding the proportions of eyes with peripapillary atrophy between groups (p < 0.09). Finally, disc size was significantly associated with VCDR (r(2) = 0.47, p < 0.01), with an increase of 0.21 in VCDR for each 1 mm(2) in disc area. CONCLUSION: Compared to normal controls, eyes with pLPC may present a higher proportion of optic nerve head findings frequently observed in glaucomatous eyes. This seems to be explained in part by the larger discs found in these eyes. We believe care should be taken while classifying them as glaucomatous or not based solely on these characteristics.

Eyes with large disc cupping and normal intraocular pressure: using optical coherence tomography to discriminate those with and without glaucoma.

We evaluated the ability of spectral-domain optic coherence tomography (SD-OCT) to differentiate large physiological optic disc cupping (LPC) from glaucomatous cupping in eyes with intraocular pressure (IOP) within the normal range. We prospectively enrolled patients with glaucoma or presumed LPC. Participants had optic discs with confirmed or suspected glaucomatous damage (defined as a vertical cup-to-disc ratio≥0.6), and all eyes had known untreated IOP<21 mmHg. For glaucomatous eyes, a reproducible glaucomatous visual field (VF) defect was required. LPC eyes required normal VF and no evidence of progressive glaucomatous neuropathy (follow-up≥30 months). Peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell complex (GCC) thicknesses were obtained using SD-OCT. For all studied parameters of pRNFL and GCC thicknesses, eyes with glaucoma (n=36) had significantly thinner values compared to eyes with LPC (n=71; P<0.05 for all comparisons). In addition, pRNFL parameters had sensitivity of 66.7% and specificity of 83.1%, and GCC parameters had sensitivity of 61.2% and specificity of 81.7%. The combination of the two analyses increased the sensitivity to 80.6%. In conclusion, while evaluating patients with large optic disc cupping and IOP in the statistically normal range, SD-OCT had only limited diagnostic ability to differentiate those with and without glaucoma. Although the diagnostic ability of the pRNFL and the GCC scans were similar, these parameters yielded an increase in sensitivity when combined, suggesting that both parameters could be considered simultaneously in these cases.

Non-pupillary block angle-closure mechanisms: a comprehensive analysis of their prevalence and treatment outcomes.

PURPOSE: To assess the prevalence and treatment outcomes of angle-closure mechanisms other than pupillary block in a population of Brazilian patients. METHODS: A retrospective chart review was conducted to evaluate patients who had undergone laser peripheral iridotomy (LPI) due to occludable angles at a single institution between July 2009 and April 2012. An occludable angle was defined as an eye in which the posterior trabecular meshwork was not visible for ≥180° on dark-room gonioscopy. Key exclusion criteria were any form of secondary glaucoma and the presence of >90° of peripheral anterior synechiae. Collected data were age, race, gender, angle-closure mechanism (based on indentation goniocopy and ultrasound biomicroscopy), intraocular pressure (IOP), number of antiglaucoma medications and subsequent management during follow-up. If both eyes were eligible, the right eye was arbitrarily selected for analysis. RESULTS: A total of 196 eyes of 196 consecutive patients (mean age 58.3 ± 11.6 years) who underwent LPI were included. In most of the patients [86% (169 patients; 133 women and 36 men]), LPI sucessfully opened the angle. Mean IOP was reduced from 18.3 ± 6.4 mmHg to 15.4 ± 4.5 mmHg after LPI (p<0.01). Among the 27 patients with persistent occludable angles, the most common underlying mechanisms were plateau iris (56%) and lens-induced component (34%). Most of these patients (85%) were treated with argon laser peripheral iridoplasty (ALPI); approximately 90% showed non-occludable angles following the laser procedure (mean IOP reduction of 18.9%), with no significant differences between patients with plateau iris and lens-induced components (p=0.34; mean follow-up of 11.4 ± 3.6 months). CONCLUSION: Our findings suggest that, in this population of Brazilian patients, several eyes with angle closure were not completely treated with LPI. In the present large case series involving middle-age patients, plateau iris was the leading cause of persistent angle closure and was effectively treated with ALPI. A detailed eye examination with indentation gonioscopy should always be performed after LPI to rule out persistent angle closure due to non-pupillary block mechanisms.