Rethinking Prophylactic Laser Peripheral Iridotomy in Primary Angle-Closure Suspects: A Review.

PURPOSE: To examine the generalizability, discuss limitations, and critically appraise recommendations on the management of primary angle-closure suspects (PACSs) that emerged as a result of recent randomized clinical trials challenging the widely accepted clinical practice of offering laser peripheral iridotomy (LPI) to PACS patients. To synthetize findings from these and other studies. DESIGN: Narrative review. SUBJECTS: Patients classified as PACS. METHODS: The Zhongshan Angle-Closure Prevention (ZAP)-Trial and the Singapore Asymptomatic Narrow Angle Laser Iridotomy Study (ANA-LIS) along with accompanying publications were reviewed. Epidemiologic studies reporting on the prevalence of primary angle-closure glaucoma and other precursor forms of the disease were also analyzed along with publications reporting on the natural course of the disease or studies reporting on outcomes after prophylactic LPI. MAIN OUTCOME MEASURES: Incidence of progression to more severe forms of angle closure. RESULTS: Patients recruited in recent randomized clinical trials are asymptomatic, do not have cataracts, may be younger, and have, on average, deeper anterior chambers depth compared with patients treated with LPI in clinics. CONCLUSIONS: The ZAP-Trial and ANA-LIS clearly represent the best available data on PACS management, additional parameters however may need to be considered when physicians face patients in clinic. PACS patients encountered at tertiary referral centers may represent more advanced cases with respect to ocular biometric parameters and may be at higher risk for disease progression compared with those recruited through population-based screening. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Survival of Visual Function in Patients with Advanced Glaucoma after Standard Guarded Trabeculectomy with MMC.

Surgical intervention in patients with severe glaucoma remains controversial, especially in unilateral cases with a minimally affected fellow eye. Many question the benefit of trabeculectomy in such cases due to high complication rates and prolonged recovery. In this retrospective, non-comparative, interventional case series we aimed to determine the effect of trabeculectomy or combined phaco-trabeculectomy on the visual function of advanced glaucoma patients. Consecutive cases with perimetric mean deviation loss worse than -20 dB were included. Survival of visual function according to five predetermined visual acuity and perimetric criteria was set as the primary outcome. Qualified surgical success utilizing two different sets of criteria commonly used in the literature constituted secondary outcomes. Forty eyes with average baseline visual field mean deviation -26.3 ± 4.1 dB were identified. The average pre-operative intraocular pressure was 26.5 ± 11.4 mmHg and decreased to 11.4 ± 4.0 mmHg (p < 0.001) after an average follow-up of 23.3 ± 15.5 months. Visual function was preserved at two years in 77% or 66% of eyes respectively according to two different sets of visual acuity and perimetric criteria. Qualified surgical success was 89%, 72% at 1 and 3 years respectively. Trabeculectomy and/or phaco-trabeculectomy is associated with meaningful visual outcomes in patients with uncontrolled advanced glaucoma.

Ab Interno Goniotomy with the Kahook Dual Blade in a Monocular Patient with Mucous Membrane Pemphigoid and Refractory Open Angle Glaucoma: A Case Report.

Purpose: To describe the case of a monocular patient with ocular mucous membrane pemphigoid (MMP) and open angle glaucoma refractory to medical treatment, who was successfully managed with ab interno goniotomy at the time of cataract surgery. Methods: A 63-year-old woman with a history of severe MMP presented with exacerbation of the disease in both eyes. Vision was 20/80 in the right eye and light perception in the left eye. Symblepharon formation, trichiasis and forniceal foreshortening were present in the right eye, while the cornea of the left eye was completely conjunctivalized. Following aggressive systemic immunosuppressive therapy with corticosteroids and cyclophosphamide, the disease was brought under control. However, the patient developed a mature cataract and high intraocular pressure (IOP) of 28 mmHg on maximal medical therapy. Due to the high risk of ocular MMP exacerbation with glaucoma filtration surgery, the decision was made to proceed with cataract extraction combined with ab interno goniotomy with the Kahook Dual Blade. Results: There were no intraoperative complications. The IOP has remained in the 12-14 mmHg range without any topical glaucoma medications over a total follow up of 3.5 years. Conclusion: Ab interno goniotomy using the Kahook Dual Blade can significantly reduce IOP and medication burden in MMP cases, where any type of conjunctival incisional surgery could induce disease flare up. In this case, it represented a safe and effective surgical procedure for ocular MMP with concomitant refractory open angle glaucoma.

Intracameral Bevacizumab Versus Sub-Tenon's Mitomycin C as Adjuncts to Trabeculectomy: 3-Year Results of a Prospective Randomized Study.

Conjunctival wound healing determines success after filtration surgery and the quest for better antifibrotic agents remains active. This study compares intracameral bevacizumab to sub-Tenon's mitomycin C (MMC) in trabeculectomy. Primary open-angle or exfoliative glaucoma patients were randomized to either bevacizumab (n = 50 eyes) or MMC (n = 50 eyes). The primary outcome measure was complete success, defined as Intraocular Pressure (IOP) > 5 mmHg and ≤21 mmHg with a minimum 20% reduction from baseline without medications. Average IOP and glaucoma medications decreased significantly in both groups at all follow-up points compared to baseline (p < 0.001), without significant difference between groups at 3 years (IOP: bevacizumab group from 29 ± 9.4 to 15 ± 3.4 mmHg, MMC group from 28.3 ± 8.7 to 15.4 ± 3.8 mmHg, p = 0.60; Medications: bevacizumab group from 3.5 ± 0.9 to 0.5 ± 1, MMC group from 3.6 ± 0.7 to 0.6 ± 1.1, p = 0.70). Complete success, although similar between groups at 3 years (66% vs. 64%), was significantly higher for bevacizumab at months 6 and 12 (96% vs. 82%, p = 0.03; 88% vs. 72%, p = 0.04, respectively) with fewer patients requiring medications at months 6, 9 and 12 (4% vs. 18%, p = 0.03; 6% vs. 20%, p = 0.04; 8% vs. 24%, p = 0.03, respectively). Complication rates were similar between groups. In conclusion, intracameral bevacizumab appears to provide similar long-term efficacy and safety results as sub-Tenon's MMC after trabeculectomy.

Heterologous, Fresh, Human Donor Sclera as Patch Graft Material in Glaucoma Drainage Device Surgery.

PURPOSE: To determine the safety and efficacy of fresh, human sclera allografts as a patch graft material in glaucoma drainage device (GDD) surgery. DESIGN: Retrospective, noncomparative, interventional, consecutive case series. SUBJECTS: All GDD cases operated between 2008 and 2013 in which fresh human corneoscleral rims were used immediately after the central corneal button was used for penetrating or endothelial keratoplasty. METHODS: Surgery was performed by 2 surgeons at 2 facilities. The Ahmed Glaucoma Valve (FP-7) was used exclusively in this cohort. Sixty-four eyes of 60 patients were identified; demographic data were recorded along with intraocular pressure (IOP), medication requirements, visual acuity, complications, and subsequent interventions. MAIN OUTCOME MEASURES: Incidence of complications. IOP and medication requirements at the last follow-up. Quilified success utilizing Tube Versus Trabeculectomy study criteria. RESULTS: The mean age of the cohort was 66.2±19.1 years; the average preoperative IOP was 33.2±11.1 mm Hg on 4.2±1.3 IOP-lowering agents before GDD surgery. IOP decreased significantly to 14.1±4.7 mm Hg (P<0.001) on 1.6±1.2 IOP-lowering agents (P<0.001) after an average follow-up of 18.2±15.4 months. There were no cases of early or late blebitis or endophthalmitis, and there was 1 case of conjunctival erosion and tube/plate exposure (1.6%) occurring 30 days after surgery. Qualified success was estimated as 90.5% and 81% at 1 and 2 years, respectively, using Tube Versus Trabeculectomy study criteria. CONCLUSIONS: Heterologous, fresh, human donor sclera appears to be a safe material for GDD tube coverage. It provides a cost-efficient alternative compared with traditional patch graft materials associated with a low risk of pathogen transmission.

Anterior chamber morphology before and after laser peripheral iridotomy determined by Scheimpflug technology in white patients with narrow angles.

PURPOSE: To investigate the changes of anterior segment morphology in patients with narrow angles using a rotating Scheimpflug camera before and after laser peripheral iridotomy (LPI). MATERIALS AND METHODS: Forty-six eyes of 46 patients classified as primary angle closure suspect, primary angle closure, primary angle closure glaucoma, acute angle closure glaucoma, fellow eyes of acute angle closure glaucoma, and iris plateau configuration were enrolled in this prospective interventional case series. Anterior chamber volume (ACV), anterior chamber depth (ACD), and anterior chamber angle (ACA) were evaluated with an Scheimpflug camera, before and after LPI. RESULTS: After LPI, the average anterior chamber depth increased from 1.88 ± 0.36 to 1.93 ± 0.32 mm (P=0.49). The mean ACV increased from 74.6 ± 25 to 89.4 ± 21.1 mm (P=0.003). The average ACA increased from 21.1 ± 4.8 to 23.4 ± 3.8 degrees (P=0.01). Eyes with synechial angle closure (primary angle closure and primary angle closure glaucoma) demonstrated a significantly smaller change in ACV compared with eyes with appositional angle closure (primary angle closure suspect). CONCLUSIONS: ACV and ACA determined by Scheimpflug technology increase to a statistically significant degree and this change appears to be more pronounced in cases of appositional angle closure.

Ab interno trabeculectomy versus trabeculectomy for open-angle glaucoma.

PURPOSE: To compare the effect of ab interno trabeculectomy with trabeculectomy. DESIGN: Retrospective, cohort study. PARTICIPANTS: A total of 115 patients who underwent ab interno trabeculectomy (study group) compared with 102 patients who underwent trabeculectomy with intraoperative mitomycin as an initial surgical procedure (trabeculectomy group). Inclusion criteria were open-angle glaucoma, age ≥ 40 years, and uncontrolled on maximally tolerated medical therapy. Exclusion criterion was concurrent surgery. METHODS: Clinical variables were collected from patient medical records. MAIN OUTCOME MEASURES: Intraocular pressure (IOP) and Cox proportional hazard ratio (HR) and Kaplan-Meier survival analyses with failure defined as IOP >21 mmHg or less than 20% reduction below baseline on 2 consecutive follow-up visits after 1 month; IOP ≤ 5 mmHg on 2 consecutive follow-up visits after 1 month; additional glaucoma surgery; or loss of light perception vision. Secondary outcome measures include number of glaucoma medications and occurrence of complications. RESULTS: Mean follow-up was 27.3 and 25.5 months for the study and trabeculectomy groups, respectively. Intraocular pressure decreased from 28.1 ± 8.6 mmHg at baseline to 15.9 ± 4.5 mmHg (43.5% reduction) at month 24 in the study group, and from 26.3 ± 10.9 mmHg at baseline to 10.2 ± 4.1 mmHg (61.3% reduction) at month 24 in the trabeculectomy group. The success rates at 2 years were 22.4% and 76.1% in the study and trabeculectomy groups, respectively (P<0.001). Younger age (P = 0.037; adjusted HR, 0.98 per year; 95% confidence interval [CI], 0.97-0.99) and lower baseline IOP (P = 0.016; adjusted HR, 0.96 per 1 mmHg; 95% CI, 0.92-0.99) were significant risk factors for failure in the multivariate analysis of the study group. With the exception of hyphema, the occurrence of postoperative complications was more frequent in the trabeculectomy group (P<0.001). More additional glaucoma procedures were performed after ab interno trabeculectomy (43.5%) than after trabeculectomy (10.8%, P<0.001). CONCLUSIONS: Ab interno trabeculectomy has a lower success rate than trabeculectomy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Acute retrobulbar optic neuritis and macular detachment associated with morning glory optic disc anomaly.

A 31-year-old woman with morning glory optic disc anomaly (MGDA) developed acute retrobulbar optic neuritis and a bullous macular detachment. MRI demonstrated truncation of the perineural space of the affected optic nerve as well as focal optic nerve enhancement. Optical coherence tomography (OCT) showed retinoschisis associated with the macular detachment. The MRI and OCT findings support the vitreous as the source of the subretinal fluid. This is the first reported case of optic neuritis in MGDA.

SPARC-null mice exhibit lower intraocular pressures.

PURPOSE: SPARC is a matricellular protein that is highly expressed in remodeling tissues, including the trabecular meshwork and ciliary body. The hypothesis for the study was that SPARC contributes to the regulation of intraocular pressure (IOP). The IOPs of SPARC-null mice, their corresponding wild-type (WT), and heterozygous animals were compared. METHODS: Diurnal and nocturnal IOPs of C57Bl/6x129SvJ WT, SPARC-null, and heterozygous mice were measured. Fluorophotometric measurements were made to assess aqueous turnover. Central corneal thickness (CCT) was measured using histology, ultrasound biomicroscopy, and optical coherence tomography. Iridocorneal angles were examined using light microscopy (LM). RESULTS: During the day, the mean IOP of SPARC-null mice (n = 142, 16.9 +/- 2.4 mm Hg) was lower than that of both WT mice (n = 104, 19.9 +/- 2.9 mm Hg; P < 10(-12)), and heterozygotes (n = 38, 19.3 +/- 2.5 mm Hg; P < 10(-4)). At night, SPARC-null mice also exhibited a blunted increase in IOP in comparison to WT and heterozygous mice. CCTs were not significantly different between WT and SPARC-null mice. Heterozygous mice tended to have thicker corneas (3.4%). Fluorophotometric measurements suggest that aqueous turnover rates in SPARC-null mice are equal to if not greater than rates in WT mice. LM of the SPARC-null iridocorneal angle revealed morphology that is indistinguishable from WT. CONCLUSIONS: SPARC-null mice have lower IOPs than do their WT counterparts with equal CCTs. The rate of aqueous turnover suggests that the mechanism is enhanced outflow resistance.

Periorbital changes associated with topical bimatoprost.

PURPOSE: To describe periorbital changes induced by chronic topical therapy with daily bimatoprost 0.03% (Lumigan, Allergan Inc., Irvine, CA, U.S.A.). METHODS: A clinical investigation of 5 nonconsecutive patients with unilateral glaucoma treated daily with topical bimatoprost 0.03% for up to 4 years prior to presentation. RESULTS: In eyes treated with bimatoprost 0.03% the authors noted periorbital fat atrophy, deepening of the upper eyelid sulcus, relative enophthalmos, loss of the lower eyelid fullness, and involution of dermatochalasis compared with the fellow untreated eye. By inspecting old photographs the authors confirmed that these unilateral changes were not present prior to starting bimatoprost. In addition, these changes were partially reversible after discontinuation of the medication, whenever that was possible. In 2 cases imaging studies confirmed the clinical impression that these findings were not related to primary orbital pathology. CONCLUSIONS: Physicians and patients should be aware of the potential of bimatoprost 0.03% to produce periorbital changes.

Efficient estimation of retinal ganglion cell number: a stereological approach.

Retinal ganglion cells (RGCs) are the only output neurons of the retina, and their degeneration after damage to the optic nerve or in glaucoma is a well established system for studying apoptosis in the central nervous system. Frequently used procedures for assessing RGC number in retinal flat mounts suffer from two problems: RGC densities are not uniform across retinal flat mounts, and density measures may therefore not reflect total number, and flat mounts do not allow efficient use of tissue. To overcome these problems we developed a stereological method for efficiently assessing RGC number in cryostat sections of the retina. We empirically demonstrate that only approximately 1:20 sections need be assessed to accurately estimate the total number of RGCs in the rat retina, providing ample tissue for additional studies in the same retina and saving considerably on more exhaustive sampling strategies. Using this method, we estimate that there are 86,282+/-4759 RGCs in the normal Brown Norway rat retina. These counts match well with estimates of axon counts in optic nerve. In a pilot study of experimental glaucoma, we determined a reduction of RGCs to 53,862+/-4272 (p<0.05). The current technique should prove advantageous to assess neuroprotective strategies in these experimental models.

Novel surgical procedures in glaucoma: advances in penetrating glaucoma surgery.

PURPOSE OF REVIEW: Despite late modifications and enhancements, traditional penetrating glaucoma surgery is not without complications and is reserved for patients in whom pharmacologic treatment and/or laser trabeculoplasty do not suffice to control the intraocular pressure. This article critically reviews recent advances in penetrating glaucoma surgery with particular attention paid to two novel surgical approaches: ab interno trabeculectomy with the Trabectome and implantation of the Ex-PRESS shunt. RECENT FINDINGS: Ab interno trabeculectomy (Trabectome) achieves a sustained 30% reduction in intraocular pressure by focally ablating and cauterizing the trabecular meshwork/inner wall of Schlemm's canal. It has a remarkable safety profile with respect to early hypotonous or infectious complications as it does not generate a bleb, but it can be associated with early postoperative intraocular pressure spikes that may necessitate additional glaucoma surgery. The Ex-PRESS shunt is more commonly implanted under a partial thickness scleral flap, and appears to have similar efficacy to standard trabeculectomy offering some advantages with respect to the rate of early complications related to hypotony. SUMMARY: Penetrating glaucoma surgery will continue to evolve. As prospective randomized clinical trials become available, we will determine the exact role of these surgical techniques in the glaucoma surgical armamentarium.

Potential impact of seatbelt use on the spectrum of ocular injuries and visual acuity outcomes after motor vehicle accidents with airbag deployment.

PURPOSE: To investigate the association between seatbelt use and (1) the spectrum of ocular injuries and (2) visual acuity outcomes after motor vehicle accidents (MVAs) with airbag deployment. DESIGN: Single-center retrospective observational case series. PARTICIPANTS: Forty-seven patients involved in MVAs with airbag deployment. METHODS: Medical record review of all patients evaluated after an MVA with airbag deployment between January, 1997, and August, 2005, at a single level 1 trauma center. MAIN OUTCOME MEASURES: Type of ocular injury and visual acuity at 3 months after an MVA. RESULTS: Seventy-one percent of patients who did not wear seatbelts experienced type III ocular injuries compared with 31% who wore seatbelts (P<0.0002). Posterior segment injuries occurred only in patients who did not wear seatbelts. At the 3-month follow-up, 76% of patients who did not wear seatbelts achieved a visual acuity of 20/40 or better compared with 96% of patients who wore seatbelts (P>0.10); a visual acuity worse than 20/200 was measured in 14% and 0% of patients in the 2 groups, respectively (P<0.03). CONCLUSIONS: In the current study, the use of seatbelts was associated with less severe ocular injuries and better visual outcomes.

Hsp27 phosphorylation in experimental glaucoma.

PURPOSE: The role of heat shock proteins (Hsp) in injury response has been well established, but it is now becoming apparent that the phosphorylation state of Hsp27 may be a critical determinant of its ability to act in a protective capacity. In this study, the expression of Hsp27 and its phosphorylation were evaluated in an experimental glaucoma model in Brown Norway rats and in a spontaneous model of glaucoma in the DBA/2J mouse. METHODS: The intraocular pressure (IOP) of one eye was elevated by injecting 1.9 M saline into the episcleral vein, as previously described in Brown Norway rats. IOP was measured in awake Brown Norway rats before surgery and every other day after saline injection. After 10 days of elevated IOP, the retinas were either removed for Western blot analysis or fixed for immunohistochemistry (IHC). IOP measurement in 7-month-old female DBA/2J mice was performed by direct cannulation. Retinas of eyes with and without elevated IOP were collected for Western blot analysis. RESULTS: Western blot results showed a significant increase in total Hsp27 (3.9-fold; P < 0.05; n = 8) and phosphorylated Hsp27 (pHsp27) (2.1-fold; P < 0.05; n = 6) in high IOP eyes in the experimental rat glaucoma model, and similar increases were observed in DBA/2J mice with elevated IOP (3.1-fold and 2.2-fold for Hsp27 and pHsp27, respectively; P < 0.05; n = 5). In rats, increased Hsp27 and pHsp27 immunoreactivity were observed in the nerve fiber layer of elevated IOP eyes and colocalized with glial fibrillary acidic protein (GFAP) and with vimentin staining, suggesting that glial cells contribute to the increase in Hsp27 and pHsp27 seen in experimental glaucoma. No change in Hsp70 or Hsp90 was observed. CONCLUSIONS: These results confirm previous reports of elevated Hsp27 in experimental glaucoma and extend them to the DBA/2J mouse. In addition, a significant increase occurred in Hsp27 phosphorylation with elevated IOP in both models of glaucoma. IHC studies show that the increases in Hsp27 and pHsp27 occur primarily in glial cells.

Apoptotic retinal ganglion cell death in the DBA/2 mouse model of glaucoma.

The DBA/2 mouse has been used as a model for spontaneous secondary glaucoma. We attempted to determine the in vivo time course and spatial distribution of retinal ganglion cells (RGCs) undergoing apoptotic death in DBA/2 mice. Female DBA/2 mice, 3, 9-10, 12, 15, and 18 months of age, received intravitreal injections of Annexin-V conjugated to AlexaFluor 1h prior to euthanasia. Retinas were fixed and flat-mounted. Annexin-V-positive RGCs in the hemiretina opposite the site of injection were counted, and their locations were recorded. Positive controls for detection of apoptotic RGCs by Annexin-V labeling included rats subjected to optic nerve ligation, and C57BL/6 mice subjected to either optic nerve ligation or intravitreal injection of NMDA. To verify that Annexin-V-labeled cells were RGCs, intravitreal Annexin-V injections were also performed on retinas pre-labeled retrogradely with FluoroGold or with DiI. Annexin-V-positive RGC locations were analyzed to determine possible clustering and areas of preferential loss. Annexin-V labeled apoptotic RGCs in eyes after optic nerve ligation, intravitreal NMDA injection, as well as in aged DBA/2 animals. In glaucomatous DBA/2 mice 95-100% of cells labeled with Annexin-V were also FluoroGold- and DiI-positive. This confirms that Annexin-V can be used to specifically detect apoptotic RGCs in rodent retinas. In DBA/2 mice, apoptotic RGC death is maximal from the 12th to the 15th month of age (ANOVA, p<0.001, Fisher's post hoc test) and occurs in clusters. These clusters are initially located in the midperipheral retina and progressively occur closer to the optic nerve head with increasing age. Retrograde axonal transport of FluoroGold in the glaucomatous mouse retina is functional until at least 2-3days prior to initiation of apoptotic RGC death.