Diabetes has no additional impact on retinal ganglion cell loss in a mouse model of spontaneous glaucoma.

PURPOSE: There is no valid medical treatment for diabetic retinopathy mostly because its pathogenesis remains largely unknown. Early stages of diabetic retinopathy, just like glaucoma, are characterized by the loss of retinal ganglion cells. Whether the two diseases may share a similar pathogenic background is unknown. METHODS: To clarify this issue the thickness of retinal nerve fiber layer was studied in vivo by optical coherence tomography in 10 Ins2Akita (diabetic) and 10 C57BL/6J (control) mice. The number of retinal ganglion cells and retina's surface covered by neurofilaments were quantified ex vivo in 12 normoglycemic DBA/2J (glaucoma) and 11 diabetic (alloxan-induced) DBA/2J mice (glaucoma + diabetes). RESULTS: At 16 weeks of age retinal nerve fiber layer was significantly thinner in Ins2Akita mice confirming the neurodegenerative impact of diabetes. Number of retinal ganglion cells and retina's surface covered by neurofilaments were similar in normoglycemic and diabetic DBA/2J mice with the exception of the superior quadrant where the number of retinal ganglion cells was increased in animals with glaucoma + diabetes. CONCLUSIONS: In presence of glaucoma, diabetes is unable to induce further retinal ganglion cells loss. The hypothesis that the mechanism leading to retinal ganglion cells loss may be shared by the two diseases cannot be ruled out. Whether early diabetes-driven retinal neurodegeneration could be prevented by neuroprotective treatment proven to be effective in case of glaucoma, remains to be clarified.

Needle revision outcomes after glaucoma filtering surgery: survival analysis and predictive factors.

PURPOSE: To evaluate the efficacy and safety of needle revision and examine factors predictive of failure. METHODS: In total, 157 eyes of 131 patients that underwent needle revision augmented with either 5-fluorouracil or betamethasone for trabeculectomy failure were included in this retrospective study. Complete failure was defined as additional glaucoma surgery, ciliodestructive procedures, loss of light perception, sight-threatening complications, hypotony maculopathy, and surgical bleb revision. Success was defined as intraocular pressure ⩽ 18 (criterion A), ⩽15 (criterion B), and ⩽12 mmHg (criterion C) reached with (qualified) or without (complete) medications, and absence of any criteria of complete failure. RESULTS: The median (interquartile range) follow-up was 25.0 (41.0) months. Complete failure rates were 19%, 26%, and 31% at 1, 2, and 3 years, respectively. For criterion A, qualified and complete success rates were, respectively, 77% and 69% at 1 year, 66% and 51% at 2 years, and 60% and 47% at 3 years. For criterion B, qualified and complete success rates were, respectively, 67% and 61% at 1 year, 48% and 42% at 2 years, and 44% and 39% at 3 years. For criterion C, qualified and complete success rates were, respectively, 43% and 41% at 1 year, 27% and 25% at 2 years, and 24% and 23% at 3 years. High baseline intraocular pressure and primary surgery were associated with higher and lower risks of complete failure, respectively. CONCLUSION: Needle revision is an effective and safe procedure to rescue failing trabeculectomy postponing or avoiding further glaucoma surgery. Eyes with low target intraocular pressure may have poor long-term outcomes.

22q11.2 microduplication syndrome and juvenile glaucoma.

BACKGROUND: 22q11.2 microduplication is a relatively recently recognized syndrome. Findings in affected individuals range from apparent normality to a wide variety of systemic and ocular conditions. We describe the association between 22q11.2 microduplication and juvenile glaucoma in two brothers. MATERIALS AND METHODS: We reviewed ophthalmological, genetic, and hematological medical records of two patients and their unaffected mother. RESULTS: A 2.07 Mb interstitial duplication in 22q11.21 and a smaller 182 kb duplication in 22q11.23 were identified in both subjects. Patient 1 showed an initial intraocular pressure (IOP) of 15 mmHg in right eye (RE) and 32 mmHg in left eye (LE) under maximum medical treatment. Deep sclerectomy surgery in LE was converted to trabeculectomy due to a macroperforation of the trabeculo-descemetic membrane. Postoperatively, the patient developed persistent hypotony with retinal folds, while IOP in RE increased to 28 mmHg. Trabeculectomy in RE was also complicated by persistent hypotony. Autologous blood injection was performed, resulting in an increase in both visual acuity and IOP. Patient 2 presented with an IOP of 29 mmHg in RE and 33 mmHg in LE. We planned an elective trabeculectomy and added orally administered acetazolamide. The patient developed bilinear cytopenia that contraindicated the surgical procedure. After hematologic normalization, the patient underwent trabeculectomy in LE, causing persistent hypotony. We performed deep sclerectomy surgery in RE, without any significant intra- or post-operative complications. CONCLUSIONS: 22q11.2 microduplication syndrome can be associated with juvenile glaucoma. Trabeculectomy may be complicated by persistent hypotony. Deep sclerectomy appears to be a better surgical option, although the presence of a thin sclera may result in conversion to trabeculectomy.

Optical Coherence Tomography Angiography Macular and Peripapillary Vessel Perfusion Density in Healthy Subjects, Glaucoma Suspects, and Glaucoma Patients.

Purpose: To evaluate macular and peripapillary vessel perfusion density (VD) in glaucoma suspects (GS) and glaucoma patients; to correlate ganglion cell-inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) thicknesses with macular and peripapillary VD; and to evaluate the diagnostic accuracy of the structural and vascular parameters. Methods: A consecutive series of GS, glaucoma patients, and healthy subjects was prospectively recruited from July 1, 2016, to January 31, 2017. All subjects underwent standard automated perimetry, spectral-domain optical coherence tomography (OCT), and 6 × 6-mm optical coherence tomography angiography (OCT-A) centered on the fovea and optic nerve. Results: Forty controls, 40 GS, and 40 glaucoma patients were enrolled. Peripapillary RNFL, GCIPL, and macular RNFL thicknesses significantly decreased in the glaucoma group compared to controls and GS (P < 0.01). Peripapillary VD in average and in the superior and inferior quadrants decreased in the glaucoma group (P ≤ 0.001); conversely, macular VD was not statistically different across groups (P > 0.05). At the peripapillary area, a correlation between RNFL thickness and VD was found; conversely, no statistically significant correlation was found between GCIPL thicknesses and macular VD (all P > 0.05) in all groups. Peripapillary RNFL and GCIPL showed higher diagnostic capacity compared to peripapillary and macular VDs. Conclusions: Structural damage is evident both in the peripapillary and in macular areas. Vascular damage seems to be less prominent, as it was seen only for the glaucoma group and at the radial peripapillary plexus. Diagnostic abilities are excellent for structural variables, less so but still good for peripapillary VD, and poor for macular VD.

Postoperative Management of Penetrating and Nonpenetrating External Filtering Procedures.

Correct postoperative management is fundamental to prevent and treat complications and to optimize the success of filtering surgery. Timely control visits and appropriate actions and prescriptions ensure the best outcomes, allow recovery from a number of untoward events, and can reestablish filtration when failure seems imminent. In contrast, a slack follow-up and wrong interventions or prescriptions can lead to the failure of any surgery, no matter how accurately it was carried out, sometimes jeopardizing vision and even the anatomy of the globe. The purpose of this review is to present a rational approach to postoperative follow-up and to synthetically describe how to prevent, recognize and address the most common complications of filtering surgery, pointing out the most common pitfalls in the management of the operated eye.

Nd:Yag laser goniopuncture for deep sclerectomy: efficacy and outcomes.

PURPOSE: To report on the safety and efficacy of Nd: YAG laser goniopuncture (LGP) for postsurgical intraocular pressure increase after deep sclerectomy (DS) in a consecutive cohort of open-angle glaucoma patients. METHODS: This case series included 56 eyes from 49 consecutive patients who underwent LGP between November 2008 and March 2015. Prior to LGP, patients had undergone DS augmented with mitomycin C and injectable cross-linked hyaluronic acid implant between October 2008 and May 2014. Demographic variables, type of glaucoma, prior phacoemulsification, intraocular pressure (IOP), best-corrected visual acuity, execution of post-LGP maneuvres, and post-LGP complications were analyzed. The success rate of the procedure was analyzed using the Kaplan-Meier survival curve. Univariate and multivariate analyses were performed using the Cox proportional hazard regression model in order to highlight variables associated with a failure to achieve surgical success. RESULTS: Mean IOP was 23.0 mmHg prior to LGP, and 12.5, 11.8, and 10.5 mmHg at 6, 12, and 24 months after LGP respectively. Post-laser IOP was significantly lower than pre-laser IOP at every time point. For an IOP ≤ 15 mmHg, success rates were 85 % at 6 months, 76 % at 1 year, and 62 % at 2 years. Thirty-eight eyes underwent prophylactic iridotomy and iridoplasty prior to LGP. Iris prolapse into the trabeculo-descemetic window following LGP occurred in 6/18 eyes (33.3 %) of the non-pretreated and in 1/38 eyes (2.6 %) of the pretreated group. One case of choroidal detachment and one delayed suprachoroidal hemorrhage occurred after LGP execution in two non-pretreated eyes. CONCLUSIONS: LGP is a relatively safe and effective complementary adjunct to deep sclerectomy that makes it possible to further lower IOP and avoid additional filtering surgery. Prophylactic iridotomy and localized iridoplasty may permit the frequency of post-LGP complications to be reduced.

Deep Sclerectomy With Mitomycin C and Injectable Cross-linked Hyaluronic Acid Implant: Long-term Results.

PURPOSE: To evaluate the long-term efficacy and safety of deep sclerectomy (DS) augmented with mitomycin C (MMC) and injectable cross-linked hyaluronic acid implant (Healaflow) in medically refractory glaucoma patients. MATERIALS AND METHODS: Our study included 96 eyes of 83 consecutive patients with open-angle glaucoma undergoing MMC-DS with injectable cross-linked hyaluronic acid implant. Mean follow-up was 28.6±20.0 months. Variables analyzed were: intraocular pressure (IOP), best-corrected visual acuity, mean number of antiglaucomatous drugs, execution of postoperative maneuvres (goniopuncture, bleb needling, and laser lysis of scleral flap sutures). Tonometric success was defined by 2 different thresholds, specifically IOP≤21 mm Hg (criterion A) and ≤15 mm Hg (criterion B). The procedure was defined as a qualified success if reached with medication and as a complete success if reached without. RESULTS: For criterion A, qualified and complete success rates were 96% and 94%, respectively, at 12 months, 95% and 92% at 24 months, and 92% and 89% at 36 months. For criterion B, qualified and complete success rates were 75% and 75%, respectively, at 12 months, 62% and 60% at 24 months, and 59% and 58% at 36 months. Goniopuncture was performed in 56 eyes (58%), bleb needling with 5-fluorouracil injection in 4 eyes (5.1%), and laser release of scleral flap sutures in 4 eyes (4%). Six eyes required additional filtering surgery. CONCLUSION: DS with Healaflow and MMC seems to be an effective and safe technique to lower IOP in patients affected by open-angle glaucoma, with few postoperative complications.

Delayed suprachoroidal hemorrhage following Nd:YAG laser goniopuncture: a case report.

PURPOSE: To report a delayed suprachoroidal hemorrhage following Nd:YAG laser goniopuncture (LGP) in an eye with a previous deep sclerectomy. METHODS: Case report. RESULTS: A 75-year-old woman with advanced primary open-angle glaucoma underwent LGP due to unsatisfactory intraocular pressure (IOP) in her left eye, 1 month after undergoing deep sclerectomy in the same eye. Delayed suprachoroidal hemorrhage occurred the day after LGP execution. CONCLUSIONS: Nd:YAG laser goniopuncture is often performed to enhance IOP control following deep sclerectomy. Although LGP is usually effective and safe, severe complications, such as delayed suprachoroidal hemorrhage, may occur after its execution.

Glaucoma: present challenges and future trends.

The authors indicate four key issues which, in their opinion, represent the most stimulating challenges in the field of glaucoma today, and describe the present approaches and the developments that can be expected or advised in the near future: (1) Glaucoma is often undiagnosed or diagnosed too late. Accurate detection is crucial to correctly recognize and treat affected subjects, thus reducing the disability and the social burden of the disease. Is glaucoma screening advisable and cost-effective? What strategies can be implemented to achieve an earlier diagnosis? (2) What role can genetics play in glaucoma clinics? (3) What are the fundamentals and the limits of medical hypotensive and nonhypotensive treatment of glaucoma today, and what novelties could be introduced in the next few years? (4) What are the current and future options for glaucoma surgery? Should we aim at reducing aqueous production or at enhancing aqueous outflow? What are the success figures and the pros and cons of ab externo procedures with external filtration (trabeculectomy, nonpenetrating techniques and glaucoma drainage devices) and of ab externo techniques with internal filtration (viscocanalostomy and canaloplasty)? Will microinvasive procedures ever play a role in the treatment of the disease? These questions and the possible future developments in the management of glaucoma are discussed critically, based on the current clinical state of the art, on a review of the literature, and on an everyday experience in a busy university hospital glaucoma service.

Visual outcome in ocular sarcoidosis: retrospective evaluation of risk factors.

PURPOSE: To analyze risk factors associated with poor visual outcome in patients with ocular sarcoidosis. METHODS: In this retrospective study, charts of 44 patients with uveitis and biopsy-proven sarcoidosis were reviewed. Ocular parameters evaluated were as follows: location, type of uveitis, visual acuity, presence of posterior synechia, iris nodules, vitritis, snowballs, chorioretinal lesions, retinal vasculitis, papillitis, macular edema, cataract, and glaucoma. Final visual acuity of the worst-seeing eye at last follow-up was the outcome considered in univariable and multivariable analyses. Visual acuity of the worst-seeing eye was stratified into 2 categories according to the threshold 20/50 (=20/50 and >20/50). RESULTS: A total of 44 patients with bilateral uveitis were studied. The majority of patients presented with panuveitis (52%), granulomatous type (61%), posterior synechia (62%). The most frequent vision-threatening complications were cystoid macular edema (56%) and cataract (56%). The median best-corrected visual acuity in the worst-seeing eye at presentation and at end of follow-up was respectively 0.4 (interquartile range [IQR] 0.26-0.80) and 0.63 (IQR 0.36-1.00). At univariable analysis, the presence of iris nodules (p=0.049), cystoid macular edema (p=0.007), and cataract (p=0.007) were clinically significant conditions for a visual outcome of 20/50 or worse in the worst-seeing eye. In multivariable analysis, cystoid macular edema (p=0.034) was the only statistically significant predictor associated with unfavorable visual outcome. CONCLUSIONS: In this study, we attempted to find risk factors related to poor visual outcome in patients with ocular sarcoidosis. The results suggest that only the presence of cystoid macular edema was significantly associated with worst visual outcome.

Anterior uveitis complicating zoledronic acid infusion.

Zoledronic acid is the most effective treatment in patients with hypercalcemia secondary to malignancy; occasionally it can be related to ocular inflammation. We report a case of severe unilateral anterior uveitis following administration of intravenous zoledronic acid in a patient with frontal hyperostosis secondary to breast cancer. The patient developed anterior uveitis 24 hours after the administration of intravenous zoledronate. The patient was treated with topical prednisone and cycloplegic eye drops, with complete recovery after one month. This report shows that, on rare occasions, zoledronic acid can be a possible cause of acute anterior uveitis.

Acanthamoeba keratitis with perforation after corneal crosslinking and bandage contact lens use.

A 32-year-old man with keratoconus developed corneal melting 5 days after riboflavin/ultraviolet-A corneal collagen crosslinking (CXL). Corneal scraping was positive for Acanthamoeba. The patient was unaware that he was wearing a bandage contact lens and repeatedly rinsed his face and eyelids with tap water. Because of corneal perforation, a large therapeutic keratoplasty à chaud was performed. Although CXL is considered a safe procedure, this case emphasizes the potential risks. We discuss the potential effects of deepithelialization, contact lens placement, instillation of topical nonsteroidal antiinflammatory drugs and anesthetic agents, and the possible role of apoptosis when performing CXL treatment for keratoconus.

Retinal sensitivity and retinal nerve fiber layer thickness measured by optical coherence tomography in glaucoma.

PURPOSE: To define the relationship between retinal light sensitivity and peripapillary retinal nerve fiber layer (RNFL) thickness as measured using the Stratus optical coherence tomograph (OCT). DESIGN: Prospective study. SETTING: Institutional. STUDY POPULATION: A total of 126 healthy subjects, 42 patients with ocular hypertension (OHT) and 64 patients with primary open-angle glaucoma (POAG) were examined by the 24/II program of the Humphrey Field Analyzer (Carl Zeiss Meditec, Inc, Dublin, California, USA), and the Fast RNFL Thickness examination of the OCT. Individual visual field (VF) test scores and peripapillary RNFL thickness measurements were grouped into six topographically corresponding sectors whose mean values were then calculated. One eye per patient was randomly chosen. MAIN OUTCOME MEASURES: The correlations between mean retinal sensitivity (expressed both in decibel and unlogged scales) and RNFL thickness were described with linear and logarithmic regression analyses. RESULTS: With reference to all 232 individuals, the equation that best explained the model was logarithmic when using the decibel scale, and either linear or logarithmic when using the unlogged scale. A statistically significant, age-adjusted correlation between function and structure was found in most sectors both using the decibel (logarithmic regression analysis r(2) 0.24 to 0.61, P < .001), and the unlogged scale (r(2) 0.37 to 0.53, P < .001 in both linear and logarithmic regression analyses). CONCLUSIONS: When using the decibel scale, the logarithmic equation may better explain the function/structure relationship between retinal sensitivity and OCT-measured RNFL thickness along a wide spectrum of glaucoma continuum. These results support the need to combine functional and structural tests in the detection of early glaucoma.