Review of Longitudinal Glaucoma Progression: 5 Years after the Shaffer Lecture.

In 2013, the senior author delivered the American Academy of Ophthalmology Robert N. Shaffer Lecture entitled "Glaucoma Changes-Reality Bites." This talk focused on describing the longitudinal structure-function relationships in glaucoma progression. The study was based on a 10-year longitudinal dataset created by calibrated measurements across multiple OCT generations with corresponding visual fields (VFs). The prior held observation was that functional damage follows structural damage. The lecture posited that structure and function change at similar times, but that current measurement technology limits our ability to detect functional abnormalities and change early in glaucoma, as well as to measure structural change late in the disease. The Shaffer lecture provided evidence that structure and function change concordantly and that any apparent discordance in the relationship was due to technologic limitations to measure glaucomatous change. Furthermore, we observed 5 longitudinal relationships of concordance and discordance that can exist with structure-function interactions. Concordance: (1) structure-structure progression, (2) structure-function tipping point, (3) structural floor tipping point. Discordance: (4) functional progression in a "stable" VF with structure-function correlation, (5) functional progression with "normal" structure. In this review article, we will review longitudinal glaucoma progression studies with long-term follow-up and discuss the clinical relevance of relationships of concordance and discordance that can exist with structure-function interactions.

Acquired Optic Pits Associated with Laser-assisted In Situ Keratomileusis: A Case Series.

PURPOSE: To present an association between acquired pits of the optic nerve (APON) and prior laser-assisted in situ keratomileusis (LASIK). MATERIALS AND METHODS: A retrospective case series of patients with an optic disc pit on clinical exam and a history of LASIK. Spectralis Optical Coherence Tomography images and Humphrey Visual Fields were reviewed from prior visits. Extended-depth optical coherence tomography was performed of the optic nerve head at subsequent visits after patients were identified. RESULTS: Seven patients, aged 45-73 years, were identified each with unilateral optic disc pits. Optic disc pits were located inferior in six patients and centrally in one patient. All demonstrated thinning on optical coherence tomography and six patients had corresponding visual field defects. Four patients identified these defects after their LASIK procedure while two patients were unaware of their reproducible visual field defects. All patients were treated with drops initially. One patient underwent laser trabeculoplasty, and three underwent a trabeculectomy after demonstrating progression on maximum tolerated medical therapy. CONCLUSION: This series describes a possible association between LASIK and APON. Given the similarity and severity of vision loss associated with the optic nerve pits in these patients after LASIK, increased awareness and caution is suggested while considering LASIK in susceptible individuals. HOW TO CITE THIS ARTICLE: Smith AK, Bussel I, Ling J, et al. Acquired Optic Pits Associated with Laser-assisted In Situ Keratomileusis: A Case Series. J Curr Glaucoma Pract 2020;14(3):106-108.

Two-year data comparison of ab interno trabeculectomy and trabecular bypass stenting using exact matching.

PURPOSE: To create a balanced comparison of ab interno trabeculectomy (AIT) (Trabectome) and trabecular bypass stenting (TBS) (iStent). SETTING: Eye and Ear Institute, Pittsburgh, Pennsylvania, Ross Eye Institute, Buffalo, New York, and Glaucoma Associates of Texas, Dallas, USA. DESIGN: Retrospective case series. METHODS: The primary outcome measure was an unmedicated intraocular pressure (IOP) of 21 mm Hg or less and the secondary measure was an unmedicated IOP reduction of 20% or more at 2 years. Patients were matched by baseline IOP, number of glaucoma medications, and glaucoma type using exact matching and by age using nearest neighbor matching. Individuals without a close match were excluded. All surgeries were combined with phacoemulsification. RESULTS: One hundred fifty-four AIT eyes and 110 TBS eyes were analyzed. Forty-eight AIT patients were exactly matched with 48 TBS patients. Both groups had a mean baseline IOP of 15.3 mm Hg ± 3.1 (SD). At 24 months, the mean IOP was 13.9 ± 3.3 mm Hg in AIT patients and 16.8 ± 2.8 mm Hg in TBS patients and the mean number of medications was 0.7 ± 1.0 and 1.7 ± 1.2, respectively (both P = .04). At 24 months, the IOP was 21 mm Hg or less without medications in 53% of AIT patients and 16.6% of TBS patients (P < .05). At that time, 17.6% of patients in the AIT group but no patient in the TBS group had an IOP reduction of 20% or more without medication. CONCLUSION: An exact matching comparison of AIT and TBS showed greater IOP reduction with fewer medications after AIT.

Training strategies and outcomes of ab interno trabeculectomy with the trabectome.

Plasma-mediated ab interno trabeculectomy with the trabectome was first approved by the US Food and Drug Administration in 2004 for use in adult and pediatric glaucomas. Since then, increased clinical experience and updated outcome data have led to its expanded use, including a range of glaucomas and angle presentations, previously deemed to be relatively contraindicated. The main benefits are a high degree of safety, ease, and speed compared to traditional filtering surgery and tube shunts. The increasing burden of glaucoma and expanding life expectancy has resulted in demand for well-trained surgeons. In this article, we discuss the results of trabectome surgery in standard and nonstandard indications. We present training strategies of the surgical technique that include a pig eye model, and visualization exercises that can be performed before and at the conclusion of standard cataract surgery in patients who do not have glaucoma. We detail the mechanism of enhancing the conventional outflow pathway and describe methods of visualization and function testing.

Rapid learning curve assessment in an ex vivo training system for microincisional glaucoma surgery.

Increasing prevalence and cost of glaucoma have increased the demand for surgeons well trained in newer, microincisional surgery. These procedures occur in a highly confined space, making them difficult to learn by observation or assistance alone as is currently done. We hypothesized that our ex vivo outflow model is sensitive enough to allow computing individual learning curves to quantify progress and refine techniques. Seven trainees performed nine trabectome-mediated ab interno trabeculectomies in pig eyes (n = 63). An expert surgeon rated the procedure using an Operating Room Score (ORS). The extent of outflow beds accessed was measured with canalograms. Data was fitted using mixed effect models. ORS reached a half-maximum on an asymptote after only 2.5 eyes. Surgical time decreased by 1.4 minutes per eye in a linear fashion. The ablation arc followed an asymptotic function with a half-maximum inflection point after 5.3 eyes. Canalograms revealed that this progress did not correlate well with improvement in outflow, suggesting instead that about 30 eyes are needed for true mastery. This inexpensive pig eye model provides a safe and effective microsurgical training model and allows objective quantification of outcomes for the first time.

Stratification of phaco-trabectome surgery results using a glaucoma severity index in a retrospective analysis.

BACKGROUND: To stratify the outcomes of phacoemulsification combined with trabectome surgery using a new glaucoma severity index. METHODS: This is a retrospective, observational cohort study that included open angle glaucoma patients with visually significant cataract that had phacoemulsification combined with trabectome surgery. Exclusion criteria were follow-up less than 12 months, any other surgeries or diagnosis of neovascular or active uveitic glaucoma. Patients were stratified into four groups according to the Glaucoma Index (GI) that incorporated preoperative intraocular pressure (IOP), number of medications and visual field status. The primary outcome measures were IOP reduction and the success rate at 12 months. We examined the relationship between GI group and IOP and medications at one year with a linear regression analysis and survival with log-rank testing. RESULTS: Of 1374 patients, a total of 498 cases with 12 month follow-up were included in the study after applying the exclusion criteria. At one year, IOP of GI groups 1 through 4 was reduced by 2.9 ± 4.4, 3.6 ± 5.0, 3.9 ± 5.3, and 9.2 ± 7.6 mmHg for. Individuals in the next higher GI group had a 1.69 ± 0.2 mmHg larger IOP decrease. The success rate was 98%, 93%, 96% and 88% at one year for GI groups 1 to 4 (p < 0.05). CONCLUSIONS: A substantial IOP reduction was seen in subjects with more advanced glaucoma suggesting that the trabecular meshwork is the primary impediment to outflow and its ablation benefits those eyes relatively more than in mild glaucoma. A larger IOP reduction can be expected in individuals with a higher GI group that indicates a clinically more challenging glaucoma.

Expanded spectral domain-OCT findings in the early detection of hydroxychloroquine retinopathy and changes following drug cessation.

PURPOSE: To report expanded SD-OCT findings of HCQ retinopathy that may assist the clinician in earlier diagnosis. To characterize structural changes of HCQ retinopathy with SD-OCT after drug cessation. METHODS: Setting: Private practice and academic institution. Patient Population: Patients at New England Eye Center and Ophthalmic Consultants of Boston in Boston, MA diagnosed with HCQ retinopathy and followed after drug cessation. Retrospective clinical data review by the Boston Image Reading Center. Main Outcome Measures: SD-OCT findings suggestive of HCQ retinopathy before parafoveal ellipsoid disruption. Change in SD-OCT morphological appearance and retinal thickness of each of the nine subfields corresponding to the Early Treatment of Diabetic Retinopathy Study areas. RESULTS: Thirty eyes with HCQ retinopathy were followed with SD-OCT after drug cessation. Findings before disruption of the parafoveal EZ included parafoveal outer nuclear layer (ONL) thinning, disruption of the parafoveal interdigitation zone, and reduced reflectivity of the parafoveal EZ. In early toxicity, 75 % developed progression after drug cessation, including disruption of the parafoveal EZ and retinal pigment epithelium and thinning of the ONL. Eyes with obvious toxicity had greater inferior outer ring thinning 12 months after drug cessation compared to early toxicity (p = 0.002, 95 % CI -2 to -8 µm). In obvious toxicity, the nasal inner subfield showed more thinning than the temporal inner subfield at 12 months after drug cessation (p = 0.018, 95 % CI -1 to -8 µm). CONCLUSIONS: Once HCQ retinopathy is diagnosed and the medication is discontinued, structural retinal changes commonly occur.

Combined analysis of trabectome and phaco-trabectome outcomes by glaucoma severity.

Prior glaucoma severity staging systems were mostly concerned with visual field function and retinal nerve fiber layer, but did not include intraocular pressure or medications to capture resistance to treatment. We recently introduced a simple index that combines pressure, medications, and visual field damage and applied it to stratify outcomes of trabectome surgery. In the analysis presented here, we combined data of trabectome alone and trabectome with same session cataract surgery to increase testing power and chances of effect discovery. This microincisional glaucoma surgery removes the primary resistance to outflow in glaucoma, the trabecular meshwork, and has been mostly used in mild glaucoma. Traditional glaucoma surgeries have a relatively high complication rate and have been reserved for more advanced disease stages. In the analysis presented here we include our data of trabectome combined with cataract surgery. This is a common practice pattern as both occur in the same age group with increasing frequency. For patients in higher glaucoma index (GI) groups, the intraocular pressure (IOP) reduction was 2.34+/-0.19 mmHg more than those in a GI group one level lower while holding everything else constant. Those who had undergone trabectome combined with phacoemulsification had an IOP reduction that was 1.29+/-0.39 mmHg less compared to those with trabectome alone. No statistically significant difference was found between genders and age groups while holding everything else constant. Hispanics had a 3.81+/-1.08 mmHg greater IOP reduction. Pseudoexfoliation and steroid glaucoma patients had an IOP reduction that was greater by 2.91+/-0.56 and 3.86+/-0.81 mmHg, respectively, than those with primary open angle glaucoma. These results suggest a role for trabectome-mediated ab interno trabeculectomy beyond mild forms of glaucoma. Additionally, the multifactorial glaucoma index demonstrates a role in staging patients when comparing glaucoma surgical modalities.

Glaucoma Surgery Calculator: Limited Additive Effect of Phacoemulsification on Intraocular Pressure in Ab Interno Trabeculectomy.

PURPOSE: To compare intraocular pressure (IOP) reduction and to develop a predictive surgery calculator based on the results between trabectome-mediated ab interno trabeculectomy in pseudophakic patients versus phacoemulsification combined with trabectome-mediated ab interno trabeculectomy in phakic patients. METHODS: This observational surgical cohort study analyzed pseudophakic patients who received trabectome-mediated ab interno trabeculectomy (AIT) or phacoemulsification combined with AIT (phaco-AIT). Follow up for less than 12 months or neovascular glaucoma led to exclusion. Missing data was imputed by generating 5 similar but non-identical datasets. Groups were matched using Coarsened Exact Matching based on age, gender, type of glaucoma, race, preoperative number of glaucoma medications and baseline intraocular pressure (IOP). Linear regression was used to examine the outcome measures consisting of IOP and medications. RESULTS: Of 949 cases, 587 were included consisting of 235 AIT and 352 phaco-AIT. Baseline IOP between groups was statistically significant (p≤0.01) in linear regression models and was minimized after Coarsened Exact Matching. An increment of 1 mmHg in baseline IOP was associated with a 0.73±0.03 mmHg IOP reduction. Phaco-AIT had an IOP reduction that was only 0.73±0.32 mmHg greater than that of AIT. The resulting calculator to determine IOP reduction consisted of the formula -13.54+0.73 × (phacoemulsification yes:1, no:0) + 0.73 × (baseline IOP) + 0.59 × (secondary open angle glaucoma yes:1, no:0) + 0.03 × (age) + 0.09 × (medications). CONCLUSIONS: This predictive calculator for minimally invasive glaucoma surgery can assist clinical decision making. Only a small additional IOP reduction was observed when phacoemulsification was added to AIT. Patients with a higher baseline IOP had a greater IOP reduction.

Coarsened Exact Matching of Phaco-Trabectome to Trabectome in Phakic Patients: Lack of Additional Pressure Reduction from Phacoemulsification.

PURPOSE: To compare intraocular pressure (IOP) after trabectome-mediated ab interno trabeculectomy surgery in phakic patients (T) and trabectome with same session phacoemulsification (PT) using Coarsened Exact Matching. Although phacoemulsification is associated with IOP reduction when performed on its own, it is not known how much it contributes in PT. METHODS: Subjects were divided into phakic T and PT. Exclusion criteria were follow-up for <12 months and additional glaucoma surgery. Demographics were compared by the Mann-Whitney U test and chi-squared test for continuous and categorical variables, respectively. Multiple imputation was utilized to avoid eliminating data with missing values. Groups were then matched using Coarsened Exact Matching based on age, race, type of glaucoma, baseline IOP, and number of preoperative glaucoma medications. Univariate linear regression was used to examine IOP reduction after surgery; those variables that were statistically significant were included in the final multivariate regression model. RESULTS: A total of 753 cases were included (T: 255, PT: 498). When all variables except for age were kept constant, there was an additional IOP reduction of 0.05±0.01 mmHg conferred for every yearly increment in age. Every 1 mmHg increase in baseline IOP correlated to an additional IOP reduction of 0.80±0.02 mmHg. Phacoemulsification was not found to be a statistically significant contributor to IOP when comparing T and PT (p≥0.05). T had a 21% IOP reduction to 15.9±3.5 mmHg (p<0.01) while PT had an 18% reduction to 15.5±3.6 mmHg (p<0.01). Number of medications decreased (p<0.01) in both groups from 2.4±1.2 to 1.9±1.3 and from 2.3±1.1 to 1.7±1.3, respectively. CONCLUSION: Phacoemulsification does not make a significant contribution to postoperative IOP or number of medications when combined with trabectome surgery in phakic patients.

Review and meta-analysis of ab-interno trabeculectomy outcomes.

We analysed all of the PubMed publications on ab-interno trabeculectomy (AIT) with the Trabectome (Neomedix, Irvine, California, USA) to determine the reduction in intraocular pressure (IOP) and medications following the procedure. For IOP outcomes, PubMed was searched for 'trabectome', 'ab interno trabeculotomy' and 'ab interno trabeculectomy' and all available papers retrieved. The meta-analysis used a random-effects model to achieve conservative estimates and assess statistical heterogeneity. To investigate complications, we included all abstracts from the American Glaucoma Society, American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery and the Association for Research in Vision and Ophthalmology. The overall arithmetic mean baseline IOP for standalone Trabectome was 26.71±1.34 mm Hg and decreased by 10.5±1.9 mm Hg (39% decrease) on 0.99±0.54 fewer medications. Defining success as IOP ≤21 with a 20% decrease while avoiding reoperation, the overall average success rate after 2 years was 46±34%. For combined phacoemulsification-Trabectome, the baseline IOP of 21±1.31 mm Hg decreased by 6.24±1.98 mm Hg (27% decrease) on 0.76±0.35 fewer medications. The success rate using the same definition at 2 years was 85±7%. The weighted mean IOP difference from baseline to study endpoint was 9.77 mm Hg (95% CI 8.90 to 10.64) standalone and 6.04 mm Hg (95% CI 4.95 to 7.13) for combined cases. Despite heterogeneity, meta-analysis showed significant and consistent decrease in IOP and medications from baseline to end point in AIT and phaco-AIT. The rate of visually threatening complications was <1%. On average, trabectome lowers the IOP by approximately 31% to a final IOP near 15 mm Hg while decreasing the number of medications by less than one, with a low rate of serious complications. After 2 years, the overall average success rate is 66%.

Bilateral central serous chorioretinopathy associated with estrogen modulator diindolylmethane.

Central serous chorioretinopathy (CSCR) is an idiopathic disease associated with states of hypercortisolism that causes fluid to collect under the retina resulting in visual impairment. The authors describe an otherwise healthy female patient who presented with headaches and blurry vision after a 2-month history of excessive daily consumption of diindolylmethane (DIM), an over-the-counter estrogen modulator medication used to treat facial acne. Imaging demonstrated asymmetric, bilateral CSCR with active leakage in the left eye. She was instructed to discontinue DIM and reported that visual improvement began 2 weeks after, with resolution to baseline after 8 weeks.

Dietary factors and the risk of glaucoma: a review.

Glaucoma is an optic neuropathy characterized by a progressive typical pattern of optic neurodegeneration and visual field loss. A relatively high proportion of glauctomatous individuals admit to interest in dietary modification in an attempt to manage their disease. Heavy caffeine consumption appears to have a transient effect on increasing intraocular pressure (IOP). This effect may be clinically insignificant for nonglaucomatous individuals, but the association warrants clinical consideration in those with the disease. Studies investigating the relationship between self-reported antioxidant intake and risk of glaucomatous disease have reported conflicting results. Preliminary studies investigating the relationship between self-reported glaucoma diagnosis and consumption of the oxidants calcium and iron suggest a possible relationship indicating increased risk of the disease with increased consumption of these dietary factors. Initial reports in the literature suggest a potential role for dietary modification in the treatment of glaucomatous optic neuropathy. Further study, with randomized controlled trials, may be necessary to further characterize these relationships.

OCT for glaucoma diagnosis, screening and detection of glaucoma progression.

Optical coherence tomography (OCT) is a commonly used imaging modality in the evaluation of glaucomatous damage. The commercially available spectral domain (SD)-OCT offers benefits in glaucoma assessment over the earlier generation of time domain-OCT due to increased axial resolution, faster scanning speeds and has been reported to have improved reproducibility but similar diagnostic accuracy. The capabilities of SD-OCT are rapidly advancing with 3D imaging, reproducible registration, and advanced segmentation algorithms of macular and optic nerve head regions. A review of the evidence to date suggests that retinal nerve fibre layer remains the dominant parameter for glaucoma diagnosis and detection of progression while initial studies of macular and optic nerve head parameters have shown promising results. SD-OCT still currently lacks the diagnostic performance for glaucoma screening.