Comparison of the Ahmed and Baerveldt Glaucoma Drainage Implants in the Treatment of Primary Congenital Glaucoma.

PURPOSE: To compare the outcomes of the Ahmed glaucoma valve (AGV) (New World Medical, Inc) with the Baerveldt glaucoma implant (BGI) (Johnson & Johnson Vision) in primary congenital glaucoma (PCG). METHODS: This was a retrospective review of children with PCG who underwent AGV or BGI implantation with a minimum follow-up of 6 months. Main outcome measures were intraocular pressure (IOP), the number of glaucoma medications, success rate, complications, and surgical revisions. RESULTS: The study included 153 eyes of 86 patients (120 eyes in the AGV group and 33 eyes in the BGI group), and the mean follow-up period was 58.7 ± 6.9 months in the AGV group and 58.5 ± 5.0 months in the BGI group. At baseline, IOP was lower in the AGV group (33 ± 6.3 vs 36.4 ± 6.1 months; P = .004) and the number of glaucoma medications was comparable between groups (3.4 ± 0.9 vs 3.6 ± 0.5 medication; P = .183). At 5 years, the mean IOP (18.4 ± 5.0 vs 16.3 ± 2.5 mm Hg; P = .004) and number of glaucoma medications (2.1 ± 1.3 vs 1.0 ± 1.0 medication; P = .001) were significantly less in the BGI group. Furthermore, the surgical success was 53.4% in the AGV group and 78.8% in the BGI group (P = .013). CONCLUSIONS: Both the AGV and BGI were successful in providing adequate IOP control in patients with PCG. Long-term follow-up showed that the BGI was associated with a lower IOP, fewer glaucoma medications, and a higher success rate. [J Pediatr Ophthalmol Strabismus. 2023;60(6):448-454.].

Intermediate Outcomes of Deep Sclerectomy in Juvenile Glaucoma.

PRCIS: In this retrospective study of patients with predominantly severe juvenile open-angle glaucoma, deep sclerectomy (DS) achieved a success rate [defined as intraocular pressure (IOP) between 5 to 18 mm Hg] of 72% at 3 years. PURPOSE: The purpose of this study was to evaluate the safety and efficacy of DS in patients with juvenile open-angle glaucoma (JOAG). METHODS: A retrospective chart review of all JOAG patients that underwent DS with mitomycin C at a tertiary care eye center during the period from May 2014 to May 2019. RESULTS: A total of 50 eyes in 37 patients were included. The mean age at the time of surgery was 27.1±11.3 years and the majority of patients (86%) had a cup-disc ratio of 0.8 to 0.9. The mean duration of follow-up was 26.1±13.4 months (range 12 to 54 mo). Mean IOP was reduced from 26.1±13.4 mm Hg at baseline to 15.2±6.4 mm Hg at the last follow-up visit (P<0.01). Moreover, the mean number of glaucoma medications decreased from 3.8±0.5 at baseline to 0.8±1.2 at the last follow-up visit (P<0.01). The cumulative probabilities of overall success (defined as IOP between 5 and 18 mm Hg) at 12, 24, and 36 months were 94%, 85%, and 72%, respectively. Hypotony occurred in 4 eyes (8%), and in one of these patients, the final visual acuity was >2 lines worse compared with presentation. No other vision-threatening complications were encountered. CONCLUSION: DS in JOAG was safe and successfully controlled IOP in most patients for 3 years.

Primary angle closure glaucoma is characterized by altered extracellular matrix homeostasis in the iris.

PURPOSE: To characterize the proteome of the iris in primary angle closure glaucoma (PACG). EXPERIMENTAL DESIGN: In this cross-sectional study, iris samples were obtained from surgical iridectomy of 48 adults with PACG and five normal controls. Peptides from iris were analysed using liquid chromatography-tandem mass spectrometry on an Orbitrap Q Exactive Plus mass spectrometer. Verification of proteins of interest was conducted using selected reaction monitoring on a triple quadrupole mass spectrometer. The main outcome was proteins with a log2 two-fold difference in expression in iris between PACG and controls. RESULTS: There were 3,446 non-redundant proteins identified in human iris, of which 416 proteins were upregulated and 251 proteins were downregulated in PACG compared with controls. Thirty-two upregulated proteins were either components of the extracellular matrix (ECM) (fibrillar collagens, EMILIN-2, fibrinogen, fibronectin, matrilin-2), matricellular proteins (thrombospondin-1), proteins involved in cell-matrix interactions (integrins, laminin, histidine-rich glycoprotein, paxillin), or protease inhibitors known to modulate ECM turnover (α-2 macroglobulin, tissue factor pathway inhibitor 2, papilin). Two giant proteins, titin and obscurin, were up- and down-regulated, respectively, in the iris in PACG compared with controls. CONCLUSIONS AND CLINICAL RELEVANCE: This proteomic study shows that ECM composition and homeostasis are altered in the iris in PACG.

Long-term outcomes of the Ahmed glaucoma valve surgery in childhood glaucoma.

PURPOSE: To report the rates of success of Ahmed glaucoma valve (AGV) surgery in early childhood glaucoma and factors associated with success. METHODS: Children with primary congenital or early childhood secondary glaucoma who underwent AGV surgery over a 10-year period (one eye per child) at a single institution were identified. Surgical failure was defined as having one or more of the following: intraocular pressure of >21 mm Hg 3 months postoperatively, reoperation for glaucoma, and vision loss to no light perception. RESULTS: A total of 178 patients were identified (median age, 5.8 ± 5.5 years): 125 with primary congenital and 53 with secondary childhood glaucoma. The success rate at 1 year was 92% (95% CI, 88%-96%); at 5 years, 64% (95% CI, 55%-73%); and at 10 years, 36% (95% CI, 25%-52%). Younger age at baseline (P = 0.003) and secondary childhood glaucoma (P = 0.045) were associated with lower success. CONCLUSIONS: The AGV is associated with high short-term success in children with primary congenital glaucoma, but the 10-year success rates are poor. Younger age and secondary childhood glaucoma may be associated with a more refractory outcome.

Surgical Outcomes of Microcatheter-assisted Trabeculotomy as a Secondary Procedure in Patients with Primary Congenital Glaucoma.

PURPOSE: To investigate the efficacy and safety of illuminated microcatheter-assisted trabeculotomy as a secondary procedure in patients with primary congenital glaucoma (PCG). METHODS: This retrospective case series included patients with PCG who underwent trabeculotomy using an illuminated microcatheter with the intent of catheterizing the full circumference of Schlemm's canal in a single procedure. Success was defined as intraocular pressure (IOP) ≤21 mmHg, with or without the use of glaucoma medications. Clinical examination data were collected for up to 36 months postoperatively. RESULTS: Surgery was performed on 16 eyes of 16 patients. The mean patient age was 75.1 ± 69.4 months (range: 4.0-216.0 months). Complete catheterization was achieved in 11 of the 16 eyes (69%), whereas partial catheterization was achieved in five of the 16 eyes (31%). All eyes had previously undergone surgery for PCG. The mean follow-up duration was 20.3 ± 9.0 months (range, 12.0-36.0 months). IOP was reduced from a mean of 31.8 ± 6.6 mmHg preoperatively to 15.6 ± 3.7 mmHg at the final follow-up (P < 0.001). The mean preoperative number of glaucoma medications was 3.9 ± 0.5, which was reduced to 1.1 ± 1.6 at the final follow-up (P = 0.001). Ten (62.5%) of the 16 eyes did not require glaucoma medication by the final follow-up. Early transient postoperative hyphema occurred in six eyes (37.5%). No other complications were noted. All corneas were clear at the final follow-up. CONCLUSION: Ab externo circumferential trabeculotomy using an illuminated microcatheter may be safe and effective as a secondary surgical option for children with PCG after unsuccessful glaucoma surgery.

Histopathologic and immunohistochemical features of capsular tissue around failed Ahmed glaucoma valves.

Impervious encapsulation around Ahmed glaucoma valve (AGV) results in surgical failure raising intraocular pressure (IOP). Dysregulation of extracellular matrix (ECM) molecules and cellular factors might contribute to increased hydraulic resistance to aqueous drainage. Therefore, we examined these molecules in failed AGV capsular tissue. Immunostaining for ECM molecules (collagen I, collagen III, decorin, lumican, chondroitin sulfate, aggrecan and keratan sulfate) and cellular factors (αSMA and TGFß) was performed on excised capsules from failed AGVs and control tenon's tissue. Staining intensity of ECM molecules was assessed using Image J. Cellular factors were assessed based on positive cell counts. Histopathologically two distinct layers were visible in capsules. The inner layer (proximal to the AGV) showed significant decrease in most ECM molecules compared to outer layer. Furthermore, collagen III (p = 0.004), decorin (p = 0.02), lumican (p = 0.01) and chondroitin sulfate (p = 0.02) was significantly less in inner layer compared to tenon's tissue. Outer layer labelling however was similar to control tenon's for most ECM molecules. Significantly increased cellular expression of αSMA (p = 0.02) and TGFß (p = 0.008) was detected within capsular tissue compared to controls. Our results suggest profibrotic activity indicated by increased αSMA and TGFß expression and decreased expression of proteoglycan (decorin and lumican) and glycosaminoglycans (chondroitin sulfate). Additionally, we observed decreased collagen III which might reflect increased myofibroblast contractility when coupled with increased TGFß and αSMA expression. Together these events lead to tissue dysfunction potentially resulting in hydraulic resistance that may affect aqueous flow through the capsular wall.

Outcomes of Ahmed Glaucoma Valve Revision in Pediatric Glaucoma.

PURPOSE: Encapsulation of the Ahmed glaucoma valve (AGV) plate is a common cause for postoperative elevation of intraocular pressure, especially in children. Many reports have described the outcomes of AGV revision in adults. However, the outcomes of AGV revision in children are poorly documented. The aim of this study was to determine the outcomes of AGV revision in children. DESIGN: Retrospective cross-sectional study. METHODS: A retrospective chart review of patients less than 15 years of age who underwent AGV revision with a minimum postoperative follow-up of 6 months was conducted. Outcome measures included reduction in intraocular pressure from baseline, survival analysis, and reduction in the number of antiglaucoma medications. Postoperative complications were also noted. Complete success was defined as an IOP of 21 mm Hg or less without medications, while qualified success was defined as having an IOP of 21 mm Hg or less with medications. RESULTS: A total of 44 eyes met the inclusion criteria. Primary congenital glaucoma was present in 39 eyes (88.6%), aphakic glaucoma in 4 eyes (9.1%), and Peters anomaly-associated glaucoma in 1 eye (2.3%). The mean number of previous surgeries was 1.4, and the mean age was 6.7 years (range, 1.9-13 years) with a median follow-up of 12 months (range, 6-24 months). The IOP was reduced from a preoperative mean of 30.4 (± 10.3) to 24.9 (± 10.6) mm Hg at 6 months postoperatively. Kaplan-Meier analysis showed that the complete success rate at 1 month was 100% followed by a rapid decline at 6 months to 38.6%, 27.7% at 1 year, and 5.5% at 2 years. Qualified success rate was 100% at 1 month followed by a 6-month and 1-year survival rate of approximately 50% and a 2-year survival rate of approximately 16%. The median survival time was 14 months. No specific risk factors for failure were identified. Visual acuity remained unchanged following revision. The most common complication was recurrence of encapsulation with elevated IOP (15.9%). Other complications included hyphema (n = 3; 6.8%), endophthalmitis (n = 1; 2.3%), wound leak (n = 1; 2.3%), and choroidal detachment (n = 2; 4.5%). CONCLUSION: Although the short-term success rate of AGV revision in children is high, with longer follow-up the success rate decreases significantly.

Lymphatic and Blood Vessel Density in Human Conjunctiva After Glaucoma Filtration Surgery.

PURPOSE: To investigate the lymphatic vascular microvessel density (LVD) and the blood vascular microvessel density (MVD) and their distribution in excised leaking blebs after mitomycin C trabeculectomy and normal conjunctiva specimens. MATERIALS AND METHODS: LVD and MVD in normal human conjunctiva (n=8) and excised blebs in the hypocellular stroma and peribleb tissue (conjunctiva adjacent to hypocellular bleb tissue) (n=8) were evaluated by immunohistochemistry using antibodies raised against Lymphatic Vessel Endothelial Receptor 1 (D2-40, lymphatic endothelium) and CD34 (vascular endothelium). LVD and MVD counts were performed by light microscopy in 5 fields at ×20 magnification by 3 observers. Differences were determined using Mann-Whitney U test (P<0.05 was considered significant). RESULTS: The leaking blebs showed typical epithelial-stromal domes with areas of acellular stroma covered by attenuated epithelium and surrounded by normal conjunctival epithelium and a dense scar-like matrix replacing the substantia propria. The LVD and MVD were significantly reduced to nil in the hypocellular conjunctival stroma of the excised blebs compared with normal conjunctiva (21.42 vs. 1.16, P<0.002 and 24.28 vs. 1, P<0.008, respectively). The LVD and MVD was also reduced (2- to 2.5-fold) in the peribleb stroma when compared with normal conjunctiva specimens. CONCLUSIONS: In this study we show reduced LCD and MVD in the hypocellular and peribleb stroma. These results may suggest a role of these vessels in an altered immune response in leaking blebs leading to an increased risk for blebitis.

Altered expression of fibrosis genes in capsules of failed Ahmed glaucoma valve implants.

PURPOSE: Ahmed glaucoma valve (AGV) implant is an aqueous shunt device used to control intraocular pressure in glaucoma. Implant failure results from impervious encapsulation of the shunt plate causing increased hydraulic resistance and raised intraocular pressure. We hypothesized that deregulation of fibrosis pathway contributes to capsular resistance. We tested this by studying fibrosis related gene expression in failed AGV implants. METHODS: Differential gene expression was examined in failed AGV capsules and compared to normal control tenon. Following total RNA extraction, 84 key genes in fibrosis pathway were examined by real-time PCR using RT2 Profiler PCR Array. Relative gene expression was calculated using ΔΔCt method. Gene specific TaqMan assays were used to validate select genes with ≥2 fold differential expression in the array expression profile. RESULTS: We observed differential expression in several genes in the fibrosis pathway. Almost half (39/84) of examined genes showed ≥2 fold differential expression in majority of capsules examined on the array. TaqMan assays for select genes including CCN2 (CTGF), THBS1, SERPINE1, THBS2, COL3A1, MMP3, and IL1A in an increased validation sample set showed significant changes in expression (p value from <0.001 to 0.022) at a high frequency in concurrence with our array results. CONCLUSIONS: Pathway-focused analyses identified candidate genes with altered expression providing molecular evidence for deregulation of the fibrosis pathway in AGV failure.

Development of a web-based glaucoma registry at King Khaled Eye Specialist Hospital, Saudi Arabia: a cost-effective methodology.

In this brief communication, we present the steps used to establish a web-based congenital glaucoma registry at our institution. The contents of a case report form (CRF) were developed by a group of glaucoma subspecialists. Information Technology (IT) specialists used Lime Survey softwareTM to create an electronic CRF. A MY Structured Query Language (MySQL) server was used as a database with a virtual machine operating system. Two ophthalmologists and 2 IT specialists worked for 7 hours, and a biostatistician and a data registrar worked for 24 hours each to establish the electronic CRF. Using the CRF which was transferred to the Lime survey tool, and the MYSQL server application, data could be directly stored in spreadsheet programs that included Microsoft Excel, SPSS, and R-Language and queried in real-time. In a pilot test, clinical data from 80 patients with congenital glaucoma were entered into the registry and successful descriptive analysis and data entry validation was performed. A web-based disease registry was established in a short period of time in a cost-efficient manner using available resources and a team-based approach.

Current surgical options for the management of pediatric glaucoma.

Currently, there are numerous choices for the treatment of pediatric glaucoma depending on the type of glaucoma, the age of the patient, and other particularities of the condition discussed in this review. Traditionally, goniotomy and trabeculotomy ab externo have been the preferred choices of treatment for congenital glaucoma, and a variety of adult procedures adapted to children have been utilized for other types of pediatric glaucoma with variable results and complications. More recently, seton implantations of different types have become more popular to use in children, and newer techniques have become available including visualized cannulation and opening of Schlemm's canal, deep sclerectomy, trabectome, and milder more directed cyclodestructive procedures such as endolaser and transcleral diode laser cyclophotocoagulation. This paper reviews the different surgical techniques currently available, their indications, results, and most common complications to allow the surgeon treating these conditions to make a more informed choice in each particular case. Although the outcome of surgical treatment in pediatric glaucoma has improved significantly, its treatment remains challenging.

Primary and secondary congenital glaucoma: baseline features from a registry at King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.

PURPOSE: To compare the demographic and clinical distribution of primary and secondary congenital glaucoma from a registry at King Khaled Eye Specialist Hospital. DESIGN: Registry-based cohort study. METHODS: Review of registry data that included new patients with congenital glaucoma seen between 2001 and 2003 (29 months); analysis of the demographic data and clinical features of primary and secondary congenital glaucoma at presentation. RESULTS: A total of 325 eyes of 180 patients were included. Most patients had primary congenital glaucoma (80%). The mean (± SD) age at presentation for primary congenital glaucoma was 3.8 ± 10.7 months and for secondary congenital glaucoma was 4.3 ± 7.9 months. Most primary congenital glaucoma and secondary congenital glaucoma patients had bilateral disease (82.6%; 74.3%). Primary congenital glaucoma was equally distributed by sex but secondary congenital glaucoma was 1.5-fold more common in male patients. A positive family history was elicited in 30%, and almost 60% had a history of consanguinity in both groups. The mean intraocular pressure and corneal diameter were comparable in both groups but the axial length was significantly longer in primary congenital glaucoma and cup-to-disc (C/D) ratio greater in secondary congenital glaucoma. In the primary congenital glaucoma group, corneal haze showed a significant relationship with most clinical parameters. In primary congenital glaucoma, a positive correlation was noted between age at presentation and increasing corneal diameter and axial length but a negative relationship was noted with C/D ratio and corneal haze, whereas for secondary congenital glaucoma only axial length was positively correlated. CONCLUSION: The congenital glaucoma registry provides unique baseline data on primary congenital glaucoma and secondary congenital glaucoma in Saudi Arabia that will enable us to better understand the disease in the Kingdom and region.

Long-term follow up of surgical repair of late bleb leaks after glaucoma filtering surgery.

PURPOSE: To study the long-term outcomes of surgical revision of leaking blebs after trabeculectomy and identify possible risk factors for failure. PATIENT AND METHODS: A retrospective, nonrandomized, noncomparative interventional study of 34 eyes with late bleb leaks after trabeculectomy that underwent bleb excision with conjunctival advancement. The primary outcome measure was successful repair and control of intraocular pressure (IOP). The other measures evaluated included change in visual acuity from baseline and complications such as recurrence of bleb leak, endophthalmitis or the need for additional antiglaucoma medication to control IOP. RESULTS: After a mean follow up of 36.2+/-23 months, the mean IOP at the last visit was 14.5+/-7.6 mm Hg. IOP in 58.8% of eyes was controlled without medication. Complications included early leaks (7/34), late recurrent or persistent leaks (1/34), and endophthalmitis (1/34). In all, 41.2% patients required additional medication at the last visit. Survival analysis at 22 months the probability of total and qualified success was 52% and 72%, respectively. However, this dropped to 10% and 15%, respectively, at 5 years. The probability of total and qualified success further dropped to 2.5% and 5% at 5 years when the IOP cut-off was lowered from 21 to 15 mm Hg. Cox regression analysis failed to identify risk factors for bleb failure. CONCLUSIONS: Surgical bleb revision seems to be effective in treating late bleb leaks with few postoperative complications. However, patients should be followed carefully as late failure of bleb function beyond 2 years is a significant possibility.

Side-effect profile of brimonidine tartrate in children.

PURPOSE: To investigate brimonidine-related side effects and the efficacy of brimonidine in lowering intraocular pressure (IOP) in children with primary infantile and secondary glaucoma. STUDY DESIGN: Single-center, prospective, interventional, noncomparative case series. PARTICIPANTS: Eighty-three children (mean age, 7.84 years) met the inclusion criteria. METHODS: Medical records were reviewed to identify children with primary infantile or other forms of secondary pediatric glaucoma from birth to 15 years who received brimonidine as adjunctive therapy for glaucoma. The parents of the children who met the inclusion criteria completed a detailed questionnaire-based interview. The children were examined to assess weight, major systemic effects, and efficacy of adjunctive brimonidine therapy. MAIN OUTCOME MEASURES: Questionnaire-based interview of parents to assess side effects of brimonidine and IOP-lowering effect of adjunctive brimonidine. RESULTS: Parents reported symptoms in 70 of 83 children (84%). The most common side effects were excessive sleepiness and lethargy (76%), eye itching and rubbing (49%), and stinging and burning of the eyes (39%). Logistic regression analysis showed a statistically significant independent association between age and weight with lethargy and sleepiness. In symptomatic patients, symptoms' frequency increased with low weight (<20 kg) and in the young (<6 years). Mean IOP reduction after initiation of brimonidine, mainly as an adjunct, was 5+/-6.7 mmHg (P<0.001). CONCLUSIONS: Side effects after the use of brimonidine in children were frequent. The weight and age of the child were important factors in predicting central nervous system side effects, especially excessive sleepiness and lethargy. Although brimonidine is effective in lowering IOP in children, alternative glaucoma therapy should be considered especially in children weighing <20 kg and those younger than 6 years.

Expression of apoptosis markers in the retinas of human subjects with diabetes.

PURPOSE: To investigate the expression of the apoptotic mediators in the retinas from human subjects with diabetes mellitus. METHODS: Ten donor eyes from five subjects with diabetes mellitus, and eight eyes from four nondiabetic subjects without known ocular disease serving as control subjects were examined. Immunohistochemical techniques were used with antibodies directed against glial fibrillary acidic protein (GFAP), caspase-3, Fas, Fas ligand (FasL), Bax, Bcl-2, survivin, p53, extracellular signal-regulated kinases (ERK1/2), and p38. RESULTS: In retinas from all subjects without diabetes, weak Bcl-2 immunoreactivity was confined to GFAP-positive glial cells in the nerve fiber layer. Weak immunoreactivity for ERK1/2 was noted in a few nuclei in the inner nuclear layer and in a few Müller cell processes. Cytoplasmic immunostaining for survivin was noted in the retinal pigment epithelial cells. There was no immunoreactivity for the other antibodies tested. All diabetic retinas showed cytoplasmic immunoreactivity for caspase-3, Fas, and Bax in ganglion cells. FasL immunoreactivity was detected in GFAP-positive cells. Upregulation of Bcl-2 immunoreactivity was noted in GFAP-positive cells in nerve fiber and ganglion cell layers, and Bcl-2 induction was noted in Müller cell processes. Strong immunoreactivity for ERK1/2 was observed in many nuclei in the inner nuclear layer in GFAP-positive cells in the nerve fiber and ganglion cell layers and numerous Müller cell processes. Survivin immunoreactivity was not altered in the diabetic retinas. There was no immunoreactivity for p53 and p38. CONCLUSIONS: Ganglion cells in diabetic retinas express several proapoptosis molecules, suggesting that these cells are the most vulnerable population. Glial cells in diabetic retinas are activated and express several antiapoptosis molecules in addition to the cytotoxic effector molecule FasL, suggesting a possible role of glial cells in induction of apoptosis in ganglion cells.