Complications and post-operative interventions in XEN45 gel stent implantation in the treatment of open angle glaucoma-a systematic review and meta-analysis.

BACKGROUND: The XEN45 Gel Stent is a subconjunctival filtering device that has demonstrated promising efficacy. This meta-analysis quantitatively evaluates reported complications and interventions after XEN45 implantation in the treatment of open angle glaucoma (OAG). METHODS: Pilot, cohort, observational studies, and randomised controlled trials that included at least ten patients undergoing ab interno or externo XEN45 surgery, with or without phacoemulsification were deemed eligible for inclusion. A meta-analysis of proportions with random-effect models was performed using the meta routine in R version 3.2.1. Outcomes included the rate of complications and post-operative interventions. RESULTS: One hundred and fifty-two studies were identified on initial literature search and 33 were included in final analysis. Numerical hypotony was the most common post-operative complication, involving 20% of patients (95% CI: 10-31%). Post-operative gross hyphema occurred in 14% (95% CI: 7-22%) and transient intra-ocular pressure (IOP) spikes (>30 mmHg) in 13% (95% CI: 4-27%). Stent exposure occurred in 1% (95% CI: 0-2%). Stent migration occurred in 1% (95% CI: 0-3%). XEN45 revision and/or a second XEN45 implantation was performed in 5% of patients (95% CI: 3-7%). Stent relocation was performed in 3% (95% CI: 1-7%). A second glaucoma procedure was performed in 11% (95% CI: 8-15%). 26% underwent one (95% CI: 17-36%), 13% underwent two (95% CI: 5-24%) while 4% underwent three (95% CI: 2-6%) bleb needling procedures. 35% of patients (95% CI: 29-40%) required at least one needling. The average rate of needling per patient was 0.38 (95% CI: 0.20-0.59). However, there is a lack of high-quality data, with 8 of the 33 studies assessed to have a moderate to high risk of bias. CONCLUSIONS: While literature suggests that XEN45 Gel Stent implantation is safe in the treatment of OAG, the overall current level of evidence is low and further studies are needed. More than a third of patients require at least one post-operative bleb needling procedure.

Prospective 12-month outcomes of combined iStent inject implantation and phacoemulsification in Asian eyes with normal tension glaucoma.

BACKGROUND: Glaucoma is the leading cause of irreversible blindness. Normal tension glaucoma (NTG) is a subset of open-angle glaucoma, demonstrating glaucomatous optic nerve damage in the absence of raised intraocular pressure (IOP). NTG is more prevalent in Asian populations. While generally slow-progressing, NTG may be associated with significant central visual field loss. In recent years, minimally invasive glaucoma surgery has been added to the armamentarium of glaucoma surgery. This prospective study aims to evaluate 12-month surgical outcomes of combined iStent inject (Glaukos Corporation, Laguna Hills, CA) implantation and phacoemulsification in Asian eyes with NTG. METHODS: This is a prospective, single-centre case series of 30 eyes followed up until 12 months after surgery. Outcome measures included IOP, number of glaucoma medications, best-corrected visual acuity (BCVA) and intra and postoperative complications. RESULTS: Mean age of subjects was 73.1 ± 6.3 years. Majority were ethnic Chinese (n = 27, 90%). Baseline medicated mean IOP was 13.8 ± 2.4 mmHg and mean number of glaucoma medications was 1.3 ± 0.7. Mean Humphrey visual field mean deviation was - 13.7 ± 7.6. The mean IOP reduction at all timepoints from postoperative month (POM) 3 onwards was statistically significant (all P < 0.05), with mean reduction of 1.2 mmHg (95% CI: 0.1-2.2, P = 0.037) by POM12. There was statistically significant reduction in mean number of medications from postoperative day (POD) 1 onwards (all P < 0.05), with mean decrease of 1.0 medication (95% CI: 0.9-1.1, P < 0.001) by POM12. By POM12, 25 (83.3%) eyes were medication-free. Three (10%) eyes had stent occlusion by iris requiring laser iridoplasty. One eye had gross hyphema which resolved on conservative management before POM1. Mean BCVA improved from the baseline 0.3 ± 0.3 logMAR to 0.1 ± 0.1 logMAR postoperatively (P < 0.001). There were no major adverse or sight-threatening events. No eyes required further glaucoma surgery during the 12-month follow-up period. CONCLUSION: Asian eyes with NTG which underwent combined iStent inject implantation and phacoemulsification demonstrated a significant and sustained reduction in IOP and glaucoma medications, up to 12 months postoperatively.

"Culture-positive exogenous endophthalmitis related to XEN45 gel stent implantation".

PURPOSE: The XEN45 gel stent implant (Allergen, CA, USA) is one of many micro-invasive surgical options available to glaucomatologists. Our case series describes the presentation, treatment, and possible risk factors of XEN45 gel stent related endophthalmitis. OBSERVATIONS: A 71 year old Chinese man and a 88 year old Caucasian woman underwent XEN45 gel stent implantation for primary open angle glaucoma. They presented with endophthalmitis at 7 and 4 months post-surgery respectively. The first patient had stent exposure with blebitis while the second patient did not show any signs of conjunctival defect, stent exposure, bleb leak nor blebitis. Both patients were treated immediately with intravitreal, topical and systemic antibiotics, followed by early vitrectomy. The implant was removed in the first, but not in the second patient. Vitreous cultures grew Streptococcus Viridans in the first patient and Haemophilus influenzae in the other. Unfortunately, the first patient eventually sustained a total retinal detachment requiring surgery and did not recover his vision. The second patient however, recovered with a good Snellen's visual acuity of 6/9 and maintenance of good intraocular pressure and bleb formation. CONCLUSIONS: Exogenous endophthalmitis related to XEN45 gel stent implantation is a rare but devastating complication. The risks factors identified were multiple post-operative procedures, bleb exposure, conjunctival defect, use of antifibrotics, blepharitis and prolonged post-operative antibiotics. XEN45 gel stent implant provides a different challenge to ophthalmologists compared to trabeculectomy as more post-operative procedures are required to prevent subconjunctival scarring. Great care should be taken to individualize the use of antifibrotics in each patient to balance the risk of subconjunctival fibrosis with the risk of infection. In patients with stent exposure we propose early closure of the conjunctiva to close off the portal of entry for pathogens and reduce the need for prophylactic topical antibiotics.

Effects of primary glaucoma on sleep quality and daytime sleepiness of patients residing at an equatorial latitude.

AIM: To investigate the impact of primary glaucoma on sleep quality and daytime sleepiness of patients. METHODS: Prospective cross-sectional study with consecutive sampling in South-East Asian population was performed. Validated questionnaires: the Pittsburg Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were administered prospectively. Subjects with non-glaucomatous optic neuropathy or concomitant retinal pathology were excluded. Glaucoma severity was based on HVF 24-2 perimetry. Binocular single vision was represented based on the better eye. Frequency of and predictive factors for poor sleep quality and excessive daytime sleepiness were compared. RESULTS: A total of 79 primary open angle glaucoma (POAG), 27 primary angle-closure glaucoma (PACG) patients, and 89 controls were recruited. PACG patients had higher median PSQI scores (P=0.004) and poorer sleep quality (P<0.001). Compared to controls, PACG patients were 3.34 times more likely to have poor sleep quality (P=0.008), which remained significant after adjustment for demographics (P=0.016) and predictive variables (P=0.013). PACG patients have poorer sleep quality when visual acuity (VA) was 6/15 or worse (P=0.009). Univariate and multivariate analysis of predictive variables for poor sleep quality and daytime sleepiness did not find statistical significance. CONCLUSION: PACG patients have poorer sleep quality but not daytime sleepiness. This is important in South-East Asian population with heavy disease burden. Evaluations on sleep disturbances can be considered to provide more holistic care.

Outcomes of Micropulse Transscleral Cyclophotocoagulation in Eyes With Good Central Vision.

PRECIS: This study is the first to report micropulse transscleral cyclophotocoagulation (MP-TSCPC) use in only good vision patients. MP-TSCPC significantly reduced intraocular pressure (IOP) and glaucoma medication use without any significant reduction in visual acuity at every postoperative follow-up point. PURPOSE: To evaluate outcomes of MP-TSCPC in eyes with baseline best-corrected visual acuity (BCVA) of ≥20/60. METHODS: A retrospective review of patients who underwent MP-TSCPC at Mayo Clinic and Ross Eye Institute from July 2016 to August 2017 with BCVA of ≥20/60, and a minimum of 3 months follow-up. RESULTS: A total of 61 eyes of 46 patients (68.80±17.12 y) underwent MP-TSCPC with a mean follow-up of 10.2±3.1 months. Mean IOP and mean number of glaucoma medications used were significantly reduced from baseline at every follow-up time point (P<0.0001). At month 12, mean IOP was reduced 40.2% from baseline with 85.4% of the patients having an IOP reduction of ≥20%, and mean glaucoma medication use reduced by 0.82±0.53 with 79.6% of the patients having a reduction of ≥1 medication. There was no significant reduction in BCVA from baseline at any follow-up point (P>0.05), except for 10 eyes with a vision loss of ≥2 lines and 5 out of 10 eyes had cataract progression. The probability of complete success (IOP range, 6 to 21 mm Hg or ≥20% IOP reduction; BCVA loss ≤2 lines, no reoperation for glaucoma) was 74.14%, 83.61%, 84.21%, and 75.0% at months 1, 3, 6, 12, respectively. The probability of qualified success (above criteria for IOP, no reoperation and BCVA loss >2 lines) was 81.03%, 91.80%, 94.74%, and 93.75% at months 1, 3, 6, 12, respectively. CONCLUSIONS: MP-TSCPC should be considered earlier in the management of glaucoma and can possibly be offered as an alternative to incisional glaucoma surgeries.

Optical Coherence Tomography Angiography of Optic Disc and Macula Vessel Density in Glaucoma and Healthy Eyes.

AIM: To study the microvascular density of the macular and optic nerve head in healthy and glaucoma subjects using optical coherence tomography angiography. METHODOLOGY: We performed a cross-sectional cohort study on healthy subjects and patients with glaucoma. The AngioVue Enhanced Microvascular Imaging System was used to capture the optic nerve head and macula images during one visit. En face segment images of the macular and optic disc were studied in layers. Microvascular density of the optic nerve head and macula were quantified by the number of pixels measured by a novel in-house developed software. Areas under the receiver operating characteristic curves (AUROC) were used to determine the accuracy of differentiating between glaucoma and healthy subjects. RESULTS: A total of 24 (32 eyes) glaucoma subjects (57.5±9.5-y old) and 29 (58 eyes) age-matched controls (51.17±13.5-y old) were recruited. Optic disc and macula scans were performed showing a greater mean vessel density (VD) in healthy compared with glaucoma subjects. The control group had higher VD than the glaucoma group at the en face segmented layers of the optic disc (optic nerve head: 0.209±0.05 vs. 0.110±0.048, P<0.001; vitreoretinal interface: 0.086±0.045 vs. 0.052±0.034, P=0.001; radial peripapillary capillary: 0.146±0.040 vs. 0.053±0.036, P<0.001; and choroid: 0.228±0.074 vs. 0.165±0.062, P<0.001). Similarly, the VD at the macula was also greater in controls than glaucoma patients (superficial retina capillary plexus: 0.115±0.016 vs. 0.088±0.027, P<0.001; deep retina capillary plexus: 0.233±0.027 vs. 0.136±0.073, P<0.001; outer retinal capillary plexus: 0.190±0.057 vs. 0.136±0.105, P=0.036; and choriocapillaris: 0.225±0.053 vs. 0.153±0.068, P<0.001. The AUROC was highest for optic disc radial peripapillary capillary (0.96), followed by nerve head (0.92) and optic disc choroid (0.76). At the macula, the AUROC was highest for deep retina (0.86), followed by choroid (0.84), superficial retina (0.81), and outer retina (0.72). CONCLUSIONS: Microvascular density of the optic disc and macula in glaucoma patients was reduced compared with healthy controls. VD of both optic disc and macula had a high diagnostic ability in differentiating healthy and glaucoma eyes.

Optical coherence tomography angiography of the macula and optic nerve head: microvascular density and test-retest repeatability in normal subjects.

BACKGROUND: Despite the potential usefulness of optical coherence tomography angiography in retinal and optic disc conditions, the reliability of the imaging modality remains unclear. This study set out to measure the microvascular density of macula and optic disc by mean of optical coherence tomography angiography and report the repeatability of the vessel density measurements. METHODS: Cross sectional observational cohort study. Subjects with normal eyes were recruited. Two sets of optical coherence tomography angiography images of macula and optic nerve head were acquired during one visit. Novel in-house developed software was used to count the pixels in each images and to compute the microvessel density of the macula and optic disc. Data were analysed to determine the measurement repeatability. RESULTS: A total of 176 eyes from 88 consecutive normal subjects were recruited. For macular images, the mean vessel density at superficial retina, deep retina, outer retina and choriocapillaries segment was OD 0.113 and OS 0.111, OD 0.239 and OS 0.230, OD 0.179 and OS 0.164, OD 0.237 and OS 0.215 respectively. For optic disc images, mean vessel density at vitreoretinal interface, radial peripapillary capillary, superficial nerve head and disc segment at the level of choroid were OD 0.084 and OS 0.085, OD 0.140 and OS 0.138, OD 0.216 and OS 0.209, OD 0.227 and OS 0.236 respectively. The measurement repeatability tests showed that the coefficient of variation of macular scans, for right and left eyes, ranged from 6.4 to 31.1% and 5.3 to 59.4%. Likewise, the coefficient of variation of optic disc scans, for right and left eyes, ranged from 14.3 to 77.4% and 13.5 to 75.3%. CONCLUSIONS: Optical coherence tomography angiography is a useful modality to visualise the microvasculature plexus of macula and optic nerve head. The vessel density measurement of macular scan by mean of optical coherence tomography angiography demonstrated good repeatability. The optic disc scan, on the other hand, showed a higher coefficient of variation indicating a lower measurement repeatability than macular scan. Interpretation of optical coherence tomography angiography should take into account test-retest repeatability of the imaging system. TRIAL REGISTRATION: National Healthcare Group Domain Specific Review Board ( NHG DSRB ) Singapore. DSRB Reference: 2015/00301.

Agreement of angle closure assessments between gonioscopy, anterior segment optical coherence tomography and spectral domain optical coherence tomography.

AIM: To determine angle closure agreements between gonioscopy and anterior segment optical coherence tomography (AS-OCT), as well as gonioscopy and spectral domain OCT (SD-OCT). A secondary objective was to quantify inter-observer agreements of AS-OCT and SD-OCT assessments. METHODS: Seventeen consecutive subjects (33 eyes) were recruited from the study hospital's Glaucoma clinic. Gonioscopy was performed by a glaucomatologist masked to OCT results. OCT images were read independently by 2 other glaucomatologists masked to gonioscopy findings as well as each other's analyses of OCT images. RESULTS: Totally 84.8% and 45.5% of scleral spurs were visualized in AS-OCT and SD-OCT images respectively (P<0.01). The agreement for angle closure between AS-OCT and gonioscopy was fair at k=0.31 (95% confidence interval, CI: 0.03-0.59) and k=0.35 (95% CI: 0.07-0.63) for reader 1 and 2 respectively. The agreement for angle closure between SD-OCT and gonioscopy was fair at k=0.21 (95% CI: 0.07-0.49) and slight at k=0.17 (95% CI: 0.08-0.42) for reader 1 and 2 respectively. The inter-reader agreement for angle closure in AS-OCT images was moderate at 0.51 (95% CI: 0.13-0.88). The inter-reader agreement for angle closure in SD-OCT images was slight at 0.18 (95% CI: 0.08-0.45). CONCLUSION: Significant proportion of scleral spurs were not visualised with SD-OCT imaging resulting in weaker inter-reader agreements. Identifying other angle landmarks in SD-OCT images will allow more consistent angle closure assessments. Gonioscopy and OCT imaging do not always agree in angle closure assessments but have their own advantages, and should be used together and not exclusively.

[Effects of lens opacity on AccuMap multifocal objective perimetry in glaucoma].

OBJECTIVE: To investigate the effect of lens opacity on the performance of the multi-focal visual evoked potential (mfVEP) test in patients with glaucoma and its relationship with the Humphrey's automated static perimetry. METHODS: This is a prospective, non-randomized study. Twenty-two patients were enrolled with moderate cataract and primary glaucoma scheduled for cataract surgery with or without glaucoma surgery. Humphrey visual field and mfVEP test were preformed before surgery and after 6 - 8 weeks of post-operation. Lens opacity was evaluated with slit lamp according to LOCS III (lens opacity classification system, version III) by the same ophthalmologist. RESULTS: The improvement of AccuMap objective visual field was noted after lens removal in glaucoma patients. The amplitude of the AccuMap was significantly (P < 0.01) increased after cataract surgery compared to pre-operation (382.6 nV +/- 146.7 nV vs 308.0 nV +/- 96.6 nV). AccuMap severity index (ASI) was significantly (P < 0.001) decreased following lens removal compared with pre-operation (48.6 +/- 42.4 vs 90.0 +/- 54.8, P < 0.001). Latency was little changed before and after surgery (1207.5 ms +/- 67.7 ms, 1191.2 ms +/- 61.9 ms, respectively, P = 0.289). There were no correlations between the changes of amplitude and the degree of lens opacity (Spearman correction, P = 0.09). For Humphrey visual field, the mean deviation (MD) of pre- and post-operative was significantly (P < 0.001) affected by lens opacity (-12.2 +/- 7.8, -9.6 +/- 8.8, respectively, P < 0.001), but pattern standard deviation (PSD) had no such changes (6.5 +/- 3.2, 6.3 +/- 4.0, respectively, P = 0.748). There were well correlated between the ASI and the MD both pre- or post-operation (Pearson correction, P = 0.013, P < 0.001), and between the ASI changes and the MD changes after lens removal (Pearson correction, P = 0.017). CONCLUSIONS: Lens opacity affects the AccuMap objective visual field in patients with glaucoma, especially the amplitude of the AccuMap. The ASI is sensitively correlated with the MD of Humphrey perimetry.

[The long-term effect of phacoemulsification combined with trabeculectomy and intraoperative 5-fluorouracil in glaucoma patients].

OBJECTIVE: This study was designed to evaluate the long-term effect of phacoemulsification, lens implantation combined with trabeculectomy augmented with 5-Fluorouracil (phaco-trab-5-Fu) in Asian glaucoma patients with primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). METHODS: This retrospective study included 71 consecutive patients who underwent phaco-trab-5-Fu in Singapore National Eye Center between January 1996 and December 1998. Patients with follow-up time less than 6 months were excluded from the study. RESULTS: The mean follow-up time was (53.1 +/- 20.9) months. Postoperative IOP was significantly lower than preoperation [(15.0 +/- 4.0) mmHg (1 mmHg = 0.133 kPa), (20.3 +/- 5.4) mmHg, respectively, P < 0.01]. Postoperative number of antiglaucoma medications was also significantly decreased than preoperation (P < 0.01). IOP of 1 to 5 years postoperation dropped significantly from that of preoperation (P < 0.01). Complete success (CS) rate of phaco-trab-5-Fu was 84.2%, 62.7%, 55.3% for 1, 3, 5 years, respectively. There were neither significant difference found in PACG group and POAG group, or in single-incision and separate-incision of CS rate. But mean IOP of last follow-up was significantly different between PACG and POAG [mean IOP (13.8 +/- 4.6) mmHg, (16.2 +/- 3.7) mmHg, respectively, P = 0.02]. According to LogMAR chart, mean preoperative visual acuity (VA) and postoperative VA were 0.75 +/- 0.40 and 0.46 +/- 0.46, respectively. Postoperative VA was significantly improved (P < 0.01). In visual field, MD were (-16.6 +/- 8.8) dB and (-17.6 +/- 10.1) dB at preoperation and postoperation, respectively. PSD were (6.2 +/- 2.9) dB and (6.5 +/- 3.2) dB correspondingly. There were no significant difference in both MD and PSD (P = 0.55, 0.64, respectively). One patient had early endophthalmitis and required vitrectomy. Two late-onset of hypotony were due to choroidal effusion and wound leak. CONCLUSIONS: Phacoemulsification combined with trabeculectomy and 5-Fu could be a successful and safe treatment for patients with cataract and primary glaucoma in a long run. There is no difference in success rate in PACG and POAG, or in single incision or separate incision in such combined surgery.

Additive effect of unoprostone and latanoprost in patients with elevated intraocular pressure.

AIMS: To assess the additive effect of unoprostone and latanoprost in patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT) METHODS: 32 patients with POAG or OHT were randomised to receive either latanoprost once daily or unoprostone twice daily for 4 weeks. After 4 weeks, all patients received both latanoprost and unoprostone for another 4 weeks. The IOP was measured at 9 am and 5 pm on the baseline, day 28, and day 56 visits, and at 9 am on day 14 and day 42 visits. The medications were given to the patients in an open label fashion. The observer was masked to the treatment given. The mean of the measurements was calculated. Safety parameters were also recorded. The additive effect of the medications was assessed by the reduction in intraocular pressure (IOP) when both medications were used, compared with when one medication was used. RESULTS: 28 patients completed both treatment periods and had IOP data available for evaluation. After 1 month of treatment, latanoprost significantly reduced IOP (mean by 6.1 (SEM 0.8) mm Hg (p<0.001) and unoprostone by 4.9 (1.0) mm Hg (p<0.001) from the baseline of 24.4 (0.6) mm Hg and 24.4 (1.1) mm Hg respectively (p = 0.18). When latanoprost once daily was given to patients treated with unoprostone, there was additional IOP lowering of 1.9 (0.6) mm Hg (p = 0.012). However, adding unoprostone to those being treated with latanoprost produced an IOP change of +0.4 (0.5) mm Hg (p = 0.42). Ocular symptoms and findings were mild and equally distributed between treatment groups, and after combined therapy. Hyperaemia and ocular irritation were the most frequently reported events. Over a third of patients experienced ocular irritation with the combination of medications. CONCLUSIONS: Latanoprost once daily causes additional IOP lowering in eyes which were being treated with unoprostone twice a day. However, there was no additional IOP lowering when unoprostone was added to eyes which were being treated with latanoprost. Both drugs were well tolerated together with few ocular adverse events.