Evidence-Based Consensus Guidelines Series for MicroPulse Transscleral Laser Therapy - Surgical Technique, Post-Operative Care, Expected Outcomes and Retreatment/Enhancements.

Purpose: To provide expert consensus and evidence-based current guidelines on treatment technique, postoperative care, expected outcomes and retreatment for MicroPulse Transscleral Laser Treatment (TLT). Methods: A comprehensive search of PubMed led to the identification and analysis of 61 studies on MicroPulse TLT. To provide guidance in areas where there was not enough available literature, a three-round Delphi method was conducted involving 10 international experts in MicroPulse TLT. Results: The response rate was 70% in the first round, 70% in the second round, and 80% in the third round of the Delphi method. Once all responses were aggregated, a live meeting was held with 90% attendance, and consensus was achieved on each of the findings detailed in this manuscript. Conclusion: Used within appropriate treatment parameters, with proper technique and patient selection, MicroPulse TLT is a safe and effective treatment for many types and severities of glaucoma. MicroPulse TLT represents a useful addition to the glaucoma armamentarium.

Comparison of success rate and intraocular pressure spikes between selective laser trabeculoplasty and micropulse laser trabeculoplasty in African American and Hispanic patients.

AIM: To examine the efficacy and safety of micropulse laser trabeculoplasty (MLT) versus selective laser trabeculoplasty (SLT) in a large cohort of primarily African American and Hispanic patients. METHODS: A single center retrospective comparative cohort review conducted at Cook County Health facilities that included patients with a diagnosis of open angle glaucoma or ocular hypertension who received an SLT or MLT procedure between January 2017 and May 2021. RESULTS: Totally 131 eyes of 99 patients were analyzed. The 77 eyes received SLT and 54 received MLT. Seven out of 77 eyes in the SLT group (9.1%) and 1 out of 54 eyes in the MLT group (1.9%) had an IOP spike (defined as > 5 mm Hg) at either 1h or 1wk after procedure (P=0.05, Chi-squared test with Haldane-Anscombe correction). The procedure failure rate at one year was 50% for SLT and 48% for MLT (P=0.31). CONCLUSION: MLT has a significantly lower incidence of pressure spikes and a similar treatment failure rate at 1-year post-procedure, demonstrating that it is a reasonable alternative compared to SLT.

Evidence-Based Consensus Guidelines Series for MicroPulse Transscleral Laser Therapy: Dosimetry and Patient Selection.

Purpose: To provide consensus-based current guidelines on optimal dosimetry and patient selection for MicroPulse Transscleral Laser Therapy (TLT) based on a review of the literature and a Delphi method. Methods: A comprehensive search of Pub Med led to the identification and analysis of 61 studies on MicroPulse TLT that contained information on laser settings and patient selection. To determine consensus in areas where there was not enough available literature, a three-round Delphi method was conducted. Results: The response rate was 90% in the first round, 90% in the second round, and 80% in the third round of the Delphi technique. Once all responses were aggregated, a live meeting was held with 80% attendance, and consensus was achieved on each of the findings detailed in this manuscript. Conclusion: Micropulse TLT is a useful addition to the glaucoma armamentarium. When used with proper surgical technique at energy settings within the boundaries described in this manuscript, MicroPulse TLT is a safe and effective treatment for many types and stages of glaucoma. Based on current knowledge and experience, the consensus recommendation of this expert panel is that the standard MicroPulse TLT settings using the revised MicroPulse P3 Probe should be 2500 mW, 31.3% duty cycle, and 4 sweeps at a sweep velocity of 20 seconds each per hemisphere. Both hemispheres avoiding the 3 and 9 clock hours should be treated. The panel also reached consensus on patient selection for MicroPulse TLT providing guidance for the use of the procedure.

Screening recommendations for diabetics.

Diabetes is one of the leading causes of morbidity and mortality in the United States. Patients with diabetes are at risk for multiple ophthalmologic complications including, but not limited to, cataracts, glaucoma, and retinopathy. Eye-exams are an important screening tool for patients with diabetes in order to prevent the more severe and vision-threatening sequela of disease. Early detection and treatment of diabetic retinopathy can result in a significant decrease in vision-loss. However, recent estimates demonstrate that few diabetic patients meet the recommended screening guidelines. Appropriate referral and follow-up is important for monitoring the ophthalmologic conditions associated with diabetes. Our purpose is to review current recommendations for ophthalmic screening for patients with diabetes in a clear and concise manor for primary care physicians.

The effect of various media and probe angles on the power output of the Cyclo G6 Glaucoma Laser System.

To evaluate the effect of various media and Iridex MicroPulse P3 (MP3) probe angles on the power output from the Cyclo G6 Glaucoma Laser (G6) System. A laser power meter was used to measure the power output (milliwatts, mW) of the Cyclo G6 System. Each of the ten trials consisted of measurements in six different media: no substrate, balanced salt solution (BSS), artificial tears (AT), tetracaine eye drop, lubricating ointment, and lidocaine gel. The output of the MP3 probe was measured at an angle of 90° and 45°, submerged in the respective media. The output was also measured with the probe held at 90° but above the medium. The mean power outputs with the probe being held at 90° to the sensor with no substrate, BSS, AT, tetracaine eye drop, lubricating ointment, and lidocaine gel were 358 ± 16.8 mW, 612 ± 14.2 mW, 613 ± 13.3 mW, 612 ± 14.0 mW, 620 ± 9.9 mW, and 610 ± 12.2 mW, respectively. These values were statistically higher than noncontact and 45° probe angles for each medium. The values between any two media (excluding no substrate) at a 90° probe angle with full contact were not statistically significant. The highest output of the G6 System was obtained with a 90° probe angle, with full contact and any of the coupling media.

Nailfold Capillary Hemorrhages: Microvascular Risk Factors for Primary Open-Angle Glaucoma.

BACKGROUND: Primary open-angle glaucoma (POAG) is associated with systemic microvascular dysfunction including hemorrhages and other abnormalities of the nailfold capillary bed. This study aimed to verify the specificity of nailfold capillary hemorrhages and other abnormalities as risk factors for POAG. METHODS: Nailfold video capillaroscopy was performed using a JH-1004 capillaroscope on the fourth and fifth digits of the nondominant hand in control (n = 277), POAG (n = 206), OHT (n = 57), and SG (n = 29) subjects. The number of hemorrhages, dilated capillaries >50 µm, and avascular zones ≥200 µm were counted and adjusted to counts per 100 capillaries. Descriptive analyses as well as univariate- and multivariable-adjusted logistic regression were performed comparing all groups with controls and POAG with OHT and SG. Subanalyses were conducted in POAG patients examining the association between nailfold capillary outcomes and previous glaucoma surgery, successful IOP control, or disease severity. RESULTS: All nailfold capillary outcomes were significantly increased in POAG, no outcomes were increased in SG, and only hemorrhages were mildly increased in OHT. Hemorrhages were significantly more frequent in POAG compared with both OHT (P < 0.0001) and SG (P=0.001). There were significant trends between higher numbers of hemorrhages and POAG compared with controls, OHT, and SG, with odds ratios of 18.3 (8.5-39.4), 9.1 (1.9-13.4), and 11.8 (1.7-7.3), respectively, for the presence of two or more hemorrhages per 100 capillaries. Hemorrhages were not significantly associated with previous glaucoma surgery, successful postoperative IOP control, or disease severity in POAG. CONCLUSIONS: These findings suggest that systemic microvascular dysfunction is frequent in POAG and occurs early in the disease process. The high specificity of nailfold hemorrhages makes them viable clinical risk factors for POAG.

Consensus recommendations for trabecular meshwork cell isolation, characterization and culture.

Cultured trabecular meshwork (TM) cells are a valuable model system to study the cellular mechanisms involved in the regulation of conventional outflow resistance and thus intraocular pressure; and their dysfunction resulting in ocular hypertension. In this review, we describe the standard procedures used for the isolation of TM cells from several animal species including humans, and the methods used to validate their identity. Having a set of standard practices for TM cells will increase the scientific rigor when used as a model, and enable other researchers to replicate and build upon previous findings.

Nailfold Capillary Abnormalities in Primary Open-Angle Glaucoma: A Multisite Study.

PURPOSE: There is considerable evidence for systemic vascular dysfunction in primary open-angle glaucoma (POAG). We performed nailfold capillary video microscopy to observe directly the nature of nonocular microvasculature abnormalities in POAG. METHODS: We enrolled 199 POAG patients and 124 control subjects from four sites. We used JH-1004 capillaroscopes to perform nailfold capillary video microscopy on the fourth and fifth digits of each subject's nondominant hand. Videos were evaluated for hemorrhages, dilated capillary loops > 50 µm, and avascular zones > 100 µm by graders masked to case status. Multivariable odds ratios (ORs) and 95% confidence intervals (CIs) for POAG were obtained by means of logistic regression analyses that were applied to data from all cases and controls. Corresponding estimates of moderate or severe POAG versus mild POAG (based on the Hodapp-Anderson-Parrish scale) were obtained among cases only. RESULTS: After controlling for demographic factors, family history of glaucoma, systemic diseases, and use of anticoagulation and antiplatelet therapy, for each 100 nailfold capillaries assessed, all types of microvascular abnormalities were significantly associated with POAG. Specifically, the presence of any dilated capillaries (OR = 2.9; 95% CI, 1.6-5.6), avascular zones (OR = 4.4; 95% CI, 1.7-11.3) and hemorrhages (OR = 12.2; 95% CI, 5.9-25.1) were associated with POAG. Among cases, the frequency of microvascular abnormalities was not associated with glaucoma severity (P ≥ 0.43). CONCLUSIONS: These data provided support for nonocular capillary bed abnormalities in POAG. Comparable vascular abnormalities in the optic nerve may render it susceptible to glaucomatous damage.

Complications of glaucoma drainage device surgery: a review.

PURPOSE: To review current literature on the complications of the use of glaucoma drainage device surgery. SUMMARY: The use of glaucoma drainage devices has increased significantly in recent years for both primary treatment of glaucoma and refractory glaucoma. The efficacy and safety of glaucoma drainage devices has been well established, so they are a viable surgical option in patients who fail medical therapy. With the increased use of these devices, understanding their complications is essential in managing these patients. The prevention and management of complications associated with glaucoma drainage device insertion has some similarities to that of a trabeculectomy. The glaucoma drainage devices have additional complications associated with the fact that hardware is left within the eye. There have been no definitive answers as to the perfect surgical technique to prevent complications but careful surgical performance, tube placement and use of a double-layered graft over the tube are likely to lead to a better outcome. The rate of complications also dictates careful follow up to identify these complications early in their process as early intervention will likely lead to better outcomes.

sCD44 overexpression increases intraocular pressure and aqueous outflow resistance.

PURPOSE: CD44 plays major roles in multiple physiologic processes. The ectodomain concentration of the CD44 receptor, soluble CD44 (sCD44), is significantly increased in the aqueous humor of primary open-angle glaucoma (POAG). The purpose of this study was to determine if adenoviral constructs of CD44 and isolated 32-kDa sCD44 change intraocular pressure (IOP) in vivo and aqueous outflow resistance in vitro. METHODS: Adenoviral constructs of human standard CD44 (Ad-CD44S), soluble CD44 (Ad-sCD44), and empty viral cDNA were injected into the vitreous of BALB/cJ mice, followed by serial IOP measurements. Overexpression of CD44S and sCD44 was verified in vitro by enzyme-linked immunosorbent assay (ELISA) and western blot analysis. Anterior segments of porcine eyes were perfused with the isolated sCD44. sCD44-treated human trabecular meshwork (TM) cells and microdissected porcine TM were examined by confocal microscopy and Optiprep density gradient with western blot analysis to determine changes in lipid raft components. RESULTS: Intravitreous injection of adenoviral constructs with either Ad-CD44S or Ad-sCD44 vectors caused prolonged ocular hypertension in mice. Eight days after vector injection, Ad-CD44S significantly elevated IOP to 28.3±1.2 mmHg (mean±SEM, n=8; p<0.001); Ad-sCD44 increased IOP to 18.5±2.6 mmHg (n=8; p<0.01), whereas the IOP of uninjected eyes was 12.7±0.2 mmHg (n=16). The IOP elevation lasted more than 50 days. Topical administration of a γ-secretase inhibitor normalized Ad-sCD44-induced elevated IOP. sCD44 levels were significantly elevated in the aqueous humor of Ad-CD44S and Ad-sCD44 eyes versus contralateral uninjected eyes (p<0.01). Anterior segment perfusion of isolated 32-kDa sCD44 significantly decreased aqueous outflow rates. Co-administration of isolated sCD44 and CD44 neutralizing antibody or of γ-secretase inhibitor significantly enhanced flow rates. sCD44-treated human TM cells displayed cross-linked actin network formation. Optiprep density gradient and western blot analysis of human TM cells treated with sCD44 showed decreased annexin 2 expression and increased phosphorylated annexin 2 and caveolin 1 expression. CONCLUSIONS: Our data suggest that sCD44 increases outflow resistance in vivo and in vitro. Viral overexpression of both CD44S and sCD44 is sufficient to cause ocular hypertension. Infusion of sCD44 in porcine anterior segment eyes significantly decreased flow rates. Notably, sCD44 enhanced cross-linked actin network formation. The elevated sCD44 levels seen in POAG aqueous humor may play an important causative role in POAG pathogenesis.

sCD44 internalization in human trabecular meshwork cells.

PURPOSE: To determine whether soluble CD44 (sCD44), a likely biomarker of primary open-angle glaucoma (POAG), is internalized in cultured human trabecular meshwork (TM) cells and trafficked to mitochondria. METHODS: In vitro, 32-kD sCD44 was isolated from human sera, biotinylated, and dephosphorylated. TM cells were incubated for 1 hour at 4°C with biotinylated albumin (b-albumin), biotin-labeled sCD44 (b-sCD44), or hypophosphorylated biotin-labeled sCD44 (-p b-sCD44) in the presence or absence of unlabeled sCD44, hyaluronic acid (HA), and a selected 10-mer HA binding peptide. The slides were warmed for 1 or 2 hours at 37°C, and 125 nM MitoTracker Red was added for the last 20 minutes of the incubation. The cells were washed, fixed, incubated with anti-biotin antibody and FITC-labeled goat anti-mouse antibody, and examined under a confocal microscope. RESULTS: TM cell membranes were positive for b-sCD44 after 4°C incubation. When the temperature was raised to 37°C, b-sCD44 or -p b-sCD44 appeared in the cytoplasm. The internalization of b-sCD44 was blocked by excess unlabeled sCD44, HA, and a 10-mer HA-binding peptide. Double label experiments with b-sCD44 or -p b-sCD44 and MitoTracker Red indicated partial overlap. The percent co-localization of MitoTracker Red at 2 hours and FITC -p b-sCD44 was 17.4% (P < 0.001) and for FITC b-sCD44 was 11.7% (P < 0.001) compared with b-albumin. The influence of putative CD44 phosphorylation sites on mitochondrial trafficking was determined by TargetP 1.1. CONCLUSIONS: sCD44 is internalized by TM cells and trafficked in part to mitochondria, which may be a factor in the toxicity of sCD44 in the POAG disease process.

Aqueous humor sCD44 concentration and visual field loss in primary open-angle glaucoma.

PURPOSE: To correlate aqueous humor soluble CD44 (sCD44) concentration, visual field loss, and glaucoma risk factors in primary open-angle glaucoma (POAG) patients. METHODS: Aqueous samples were obtained by paracentesis from normal and glaucoma patients who were undergoing elective surgery and analyzed for sCD44 concentration by enzyme-linked immunosorbent assay. RESULTS: In normal aqueous (n=124) the sCD44 concentration was 5.88+/-0.27 ng/mL, whereas in POAG aqueous (n=90) the sCD44 concentration was 12.76+/-0.66 ng/mL, a 2.2-fold increase (P<0.000001). In POAG patients with prior successful filtration surgery (n=13), the sCD44 concentration was decreased by 43% to 7.32+/-1.44 (P=0.001) in comparison with POAG patients without filtration surgery; however, the sCD44 concentration in the prior successful filtration subgroup with no medications and normal intraocular pressure was 12.62+/-3.81 (P=0.05) compared with normal. The sCD44 concentration of normal pressure glaucoma patients was 9.19+/-1.75 ng/mL, a 1.6-fold increase compared with normal (P=0.02). Race and intraocular pressure pulse amplitude were significant POAG risk factors in this cohort of patients. In both normal and POAG patients with mild and moderate visual field loss, sCD44 concentration was greater in African Americans than in whites (P=0.04). CONCLUSIONS: sCD44 concentration in the aqueous of POAG patients correlated with the severity of visual field loss in all stages in white patients and in mild to moderate stages in African American patients. sCD44 concentration in aqueous is a possible protein biomarker of visual field loss in POAG.