Early Postoperative Aqueous Suppression Therapy and Surgical Outcomes of Ahmed Tube Shunts in Refractory Glaucoma.

PURPOSE: To compare early vs. delayed use of aqueous suppressants on Ahmed glaucoma valve (AGV) outcomes. DESIGN: Single-center retrospective comparative case series. PARTICIPANTS: Patients who underwent AGV surgery at Wills Eye Hospital in the period between 2016 and 2021. METHODS: Retrospective review of AGV surgery at Wills Eye Hospital 2016 to 2021 for refractory glaucoma. Two groups were created: group 1 or those who received early aqueous suppressant therapy in the first 2 weeks postoperatively whenever the intraocular pressure (IOP) was > 10 mmHg, and group 2 or those who received delayed treatment after 2 weeks whenever the IOP exceeded the target pressure. Aqueous suppressant therapy included topical beta blockers, carbonic anhydrase inhibitors, and/or alpha agonists. MAIN OUTCOME MEASURES: The primary outcome measures were the frequency of hypertensive phase (HP) defined as IOP > 21 mmHg in first 3 months after an initial reduction to 21 mmHg or less in the first postoperative week not caused by tube obstruction or retraction, and month-12 surgical failure defined as 5 ≥ IOP > 21 mmHg on 2 consecutive visits, vision decline to no light perception (NLP), or glaucoma reoperation. Secondary outcome measures included changes in visual acuity (VA), IOP, and glaucoma medications at 12 months. Predictive factors for surgical failure were also identified. RESULTS: A total of 407 eyes of 391 patients (260 in group 1, 147 in group 2) with similar baseline characteristics were included. Hypertensive phase was more common in group 2 than 1 (41.5% vs. 18.5%; P < 0.001). At month 12 (N = 303 eyes), group 1 was less likely to fail than group 2 (21.2% vs. 36.8%, P = 0.003). Multivariate regression analysis showed that HP (odds ratio [OR] = 10.47, P < 0.001), delayed aqueous suppression use (OR = 2.17, P = 0.003), and lower baseline VA (OR = 1.56, P = 0.015) were the strongest predictors of month-12 failure. CONCLUSIONS: Early use of aqueous suppressants may lower the risk of HP and improve AGV outcomes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Abnormal multifocal ERG findings in patients with normal-appearing retinal anatomy.

To evaluate eyes with abnormal visual fields and multifocal electroretinograms (mfERGs) but normal-appearing frequency-domain optical coherence tomography (fdOCT) scans, the thicknesses of the outer retinal layers were measured. A total of 25 eyes from 17 patients, including 15 eyes previously tested (Dale et al. in Doc Ophthalmol 120(2):175-186, 2009) were examined. All patients were evaluated with standard automated perimetry (SAP) using the 24-2 and/or 10-2 program (Zeiss Meditec), mfERG with 103 hexagons (Veris, EDI), and fdOCT imaging (3DOCT-2000, Topcon) with scans of the macula. All patients had reliable visual fields showing macular defects and good quality mfERG and fdOCT results. The mfERG results were classified as abnormal based on decreased amplitudes and/or increased latencies corresponding to the abnormal visual field. Based on visual inspection, three experienced observers classified the fdOCT scans as normal or inconclusive, as opposed to clearly abnormal. Retinal layers of the fdOCT scans were manually segmented with the aid of a computer program and compared to mean thicknesses from 20 controls. The thicknesses of the outer segment plus retinal pigment epithelium, total receptor, and inner nuclear layers were measured. Quantitative analysis of fdOCT scans demonstrated thinning of the outer retina in some scans that was not readily apparent on visual inspection. One or more of the outer retinal layers was significantly thinner in 15 of the 25 eyes. The absence of significant thinning in the other 10 eyes represents instances in which functional loss measured by visual fields and mfERGs can precede clear structural changes on fdOCT.

Reliability of a computer-aided manual procedure for segmenting optical coherence tomography scans.

PURPOSE: To assess the within- and between-operator agreement of a computer-aided manual segmentation procedure for frequency-domain optical coherence tomography scans. METHODS: Four individuals (segmenters) used a computer-aided manual procedure to mark the borders defining the layers analyzed in glaucoma studies. After training, they segmented two sets of scans, an Assessment Set and a Test Set. Each set had scans from 10 patients with glaucoma and 10 healthy controls. Based on an analysis of the Assessment Set, a set of guidelines was written. The Test Set was segmented twice with a ≥1 month separation. Various measures were used to compare test and retest (within-segmenter) variability and between-segmenter variability including concordance correlations between layer borders and the mean across scans (n = 20) of the mean of absolute differences between local border locations of individual scans, MEAN{mean( ΔLBL )}. RESULTS: Within-segmenter reliability was good. The mean concordance correlations values for an individual segmenter and a particular border ranged from 0.999 ± 0.000 to 0.978 ± 0.084. The MEAN{mean( ΔLBL )} values ranged from 1.6 to 4.7 µm depending on border and segmenter. Similarly, between-segmenter agreement was good. The mean concordance correlations values for an individual segmenter and a particular border ranged from 0.999 ± 0.001 to 0.992 ± 0.023. The MEAN{mean( ΔLBL )} values ranged from 1.9 to 4.0 µm depending on border and segmenter. The signed and unsigned average positions were considerably smaller than the MEAN{mean( ΔLBL )} values for both within- and between-segmenter comparisons. Measures of within-segmenter variability were only slightly larger than those of between-segmenter variability. CONCLUSIONS: When human segmenters are trained, the within-and between-segmenter reliability of manual border segmentation is quite good. When expressed as a percentage of retinal layer thickness, the results suggest that manual segmentation provides a reliable measure of the thickness of layers typically measured in studies of glaucoma.

A comparison of multifocal ERG and frequency domain OCT changes in patients with abnormalities of the retina.

To compare the ability of the multifocal electroretinogram (mfERG) and frequency domain optical coherence tomography (fdOCT) to detect retinal abnormalities. A total of 198 eyes (100 patients) were referred by neuro-ophthalmologists to rule out a retinal etiology of visual impairment. All patients were evaluated with static automated perimetry (SAP) (Humphrey Visual Field Analyzer; Zeiss Meditec), mfERG (Veris, EDI) and fdOCT (3D-OCT 1000, Topcon). The mfERG was performed with 103 scaled hexagons and procedures conforming to ISCEV standards (Hood DC et al. (2008) Doc Ophthalmol 116(1):1-11). The fdOCT imaging included horizontal and vertical line scans through the fovea. Local mfERG and fdOCT abnormalities were compared to local regions of visual field sensitivity loss measured with SAP and categorized as normal/inconclusive or abnormal. 146 eyes were categorized as normal retina on both fdOCT and mfERG. The retina of 52 eyes (36 patients) was categorized as abnormal based upon mfERG and/or fdOCT. Of this group, 25 eyes (20 patients) were abnormal on both tests. However, 20 eyes (13 patients) were abnormal on mfERG, while the fdOCT was normal/inconclusive; and 7 eyes (7 patients) had normal or inconclusive mfERG, but abnormal fdOCT. Considerable disagreement exists between these two methods for detection of retinal abnormalities. The mfERG tends to miss small local abnormalities that are detectable on the fdOCT. On the other hand, the fdOCT can appear normal in the face of clearly abnormal mfERG and SAP results. While improved imaging and analysis may show fdOCT abnormalities in some cases, in others early damage may not appear on structural tests.

Correlation of echographic and photographic assessment of optic nerve head cupping in children.

PURPOSE: To determine the diagnostic value of B-scan echography in optic nerve head (ONH) cupping estimation in children. METHODS: The medical records of pediatric patients who had previously undergone examination under anesthesia and for whom both adequate B-scan echography images and optic nerve head (ONH) photographs and were available were reviewed retrospectively. The cup:disk ratio was estimated with a grading scale of 0-1.0 and rounded to the nearest tenth; degree of cupping was estimated from B-scan echography (small, medium, or large) by 5 masked graders (3 glaucoma specialists and 2 ophthalmic sonographers) on 2 separate occasions. Inter- and intraobserver agreement in echographic and photographic cupping assessment by the masked graders as well as correlation of echographic and photographic cup size estimation was evaluated. RESULTS: A total of 36 children were included. Glaucoma specialists reliably assessed cup:disk ratio with moderately good consistency across specialists (average intraclass correlation coefficient [ICC] for intraobserver agreement, 0.86; average ICC for interobserver agreement, 0.71). Sonographers were extremely reliable in assessment of cup size when examining echographic images (ICC for both inter- and intrarater variability, 1.0). Echographic estimate of cup size correlated poorly with cup:disk ratio (ICC, 0.34). CONCLUSIONS: B-scan echography is a reliable and consistent diagnostic tool in estimating the degree of ONH cupping in children and can be very useful in patients in whom direct visualization is not feasible. Failure to account for disk size may have contributed to the poor correlation between echographic cup size and photographic cup:disk ratio.

Methods to characterize lymphoid apoptosis in a murine model of autoreactivity.

The immune system is shaped by the random generation of lymphocytes followed by apoptosis of self-reactive cells, a process termed negative selection. The survival of these pathogenic cells in the periphery can elicit autoreactivity. We describe the development of a biomarker assay for the detection of pathogenic subpopulations of lymphoid cells in adult non-obese diabetic (NOD) mice based on disease-specific alterations in spontaneous or triggered cell death. Utilizing improved methods of cell separations, two distinct lymphoid cell subpopulations with increased susceptibility to apoptosis were identified and quantified. A subpopulation of CD8+ T cells that constitutes approximately 3-7% of the total CD8+ T cell population underwent apoptosis on exposure to low concentrations of TNF-alpha. Such cells were exclusively detected only in NOD mice with histologic signs of active autoreactivity. The non-T cell compartment of NOD immune system, although resistant to TNF-alpha-induced apoptosis, contained a subpopulation of B cells with spontaneous death by culture alone. The refined detection of small numbers of lymphoid cell subsets with quantifiable differences in apoptosis provides a possible immune biomarker for monitoring disease activity or treatment interventions.

A review of the iStent(®) trabecular micro-bypass stent: safety and efficacy.

There is a significant demand for procedures that can effectively treat glaucoma with low risk and good visual outcomes. To fill this void, procedures termed "minimally invasive glaucoma surgery", are gaining in popularity. This review will focus on the safety and efficacy of one such minimally invasive glaucoma surgery procedure, the trabecular micro-bypass stent. This stent is intended to lower intraocular pressure by directly cannulating Schlemm's canal and thereby enhancing aqueous outflow. Recent randomized controlled trials and case series have demonstrated the micro-bypass stent to be a relatively safe procedure, with limited complications and no serious adverse sequelae. The most common complication across all studies was stent obstruction or malposition, which generally did not result in any adverse outcome in vision or pressure control. In addition, increased rates of hypotony, choroidal hemorrhage, or infection were not seen with the micro-bypass stent in comparison to cataract surgery alone.

Islet regeneration during the reversal of autoimmune diabetes in NOD mice.

Nonobese diabetic (NOD) mice are a model for type 1 diabetes in humans. Treatment of NOD mice with end-stage disease by injection of donor splenocytes and complete Freund's adjuvant eliminates autoimmunity and permanently restores normoglycemia. The return of endogenous insulin secretion is accompanied by the reappearance of pancreatic beta cells. We now show that live donor male or labeled splenocytes administered to diabetic NOD females contain cells that rapidly differentiate into islet and ductal epithelial cells within the pancreas. Treatment with irradiated splenocytes is also followed by islet regeneration, but at a slower rate. The islets generated in both instances are persistent, functional, and apparent in all NOD hosts with permanent disease reversal.