Translating Minimally Invasive Glaucoma Surgery Devices.

Glaucoma is the leading cause of irreversible blindness with over 70 million people affected worldwide. The surgical management of glaucoma aims to lower intraocular pressure by increasing aqueous outflow facility. The latest manufacturing techniques have allowed for the development of a number of novel implantable devices to improve safety and outcomes of glaucoma surgery. These are collectively referred to as minimally invasive glaucoma surgery (MIGS) devices and are among the smallest devices implanted in the human body. This review discusses the design criterion and constraints as well as the user requirements for MIGS devices. We review how recent devices have attempted to meet these challenges and give our opinion as to the necessary characteristics for the development of future devices.

Novel approaches to model effects of subconjunctival blebs on flow pressure to improve clinical grading systems after glaucoma drainage surgery.

Clinical grading systems following glaucoma filtration surgery do not include any effects of the bleb on the intra-ocular pressure and are relatively subjective, therefore carrying the risk of inter and/or intra-observer variability. The main objective of the study is to quantify and model the effect of subconjunctival bleb on flow pressure for assessment of clinical grading following glaucoma surgery. Subconjunctival bleb was created by inserting a tube into ex vivo rabbit eyes via an ab externo approach through the anterior chamber and exiting into the subconjunctival space. Sterile dyed water was injected through the tube into the developing bleb. For the in vitro approach a silicone bleb was created by clamping a circular silicone sheet, injecting dyed water through a fixed resistance outlet tube. Photographic measurements of the bleb height, planform area and pressure were taken as a function of time. Clinical blebs were also collected over a few months. Mathematical algorithm software was used to build the bleb model. Bleb height and volume increase as pressure in the bleb increases. The bleb planform area tended to a constant determined by the section of conjunctiva prior to shunt insertion. These increases were in accordance with the bleb model developed in the Appendix. They show that the pressure in the bleb is related to the resistance of the outflow. The linearity of clinical grading systems is reviewed and a new grading approach is proposed. The pressure in the bleb has a strong dependence on bleb extent, height and a weak dependence on conjunctival thickness. The pressure in a bleb can be estimated from bleb height, radius, and flow rate inlet in agreement with the bleb flow model. These results provide support for an improved bleb categorization system.

The Implications of an Ab Interno Versus Ab Externo Surgical Approach on Outflow Resistance of a Subconjunctival Drainage Device for Intraocular Pressure Control.

PURPOSE: Minimally invasive glaucoma surgery (MIGS) devices that drain into the subconjunctival space can be inserted via an ab externo or ab interno approach. Limited experimental data exists as to the impact of either technique on intraocular pressure (IOP) control. We performed microfluidic studies by using ex vivo rabbit eyes to assess the effect of each approach on outflow resistance of a subconjunctival drainage device for IOP control. METHODS: A microfluidic experiment system was designed, consisting of a controlled reservoir of water connected to a pressure pump/flow sensor. The flow rate of water was fixed at 2 µl/min to simulate aqueous humor production. The pressure readings for each approach were recorded at a frequency of 1 Hz. A baseline reading was made before tube insertion into the eye (PEEK tube length set to aim for an initial outflow resistance of 5 to 10 mm Hg/µL/min) followed by measurements for a cumulative 2-ml volume entering the subconjunctival space. Results were adjusted for water viscosity at 37°C and reported as outflow resistance (mm Hg/µL/min ± standard error of mean). RESULTS: Outflow resistance via the ab interno approach was 90.4% higher than with the ab externo approach being measured at 0.80 ± 0.11 mm Hg/µL/min and 0.42 ± 0.05 mm Hg/µL/min, respectively. Bleb formation was observed to be less predictable with the ab interno approach. CONCLUSIONS: The ab interno approach demonstrated greater outflow resistance and less predictable bleb formation than the ab externo approach. These results have implications for long-term IOP control and success depending on the approach to device insertion and could be an important consideration for future MIGS devices. TRANSLATIONAL RELEVANCE: The effect of the ab interno versus ab externo approach of a MIGS device inserted into the subconjunctival space was assessed. The ab interno approach demonstrated greater outflow resistance and less predictable bleb formation that may have implications for the development of future MIGS devices.

A Case Report of Complete Blockage of a Baerveldt Glaucoma Implant Following Insertion of a 3-0 Supramid Suture.

PURPOSE: The aim of this study was to present a case of a Baerveldt glaucoma implant lumen being completely occluded with a 3-0 Supramid stent suture. PATIENT AND METHODS: The patient underwent Baerveldt glaucoma implant surgery with placement of an intraluminal 3-0 Supramid stent suture that acts to restrict flow across the device and reduce the risk of postoperative hypotony. Following suturing of the implant to the sclera, the device was flow tested. No flow was observed through the device tube and a significant ballooning of the tube diameter occurred with increased pressure on the device. The device was explanted from the eye and replaced with a different implant without further postoperative complication. The explanted device was assessed using custom microfluidic equipment in an in vitro environment. RESULTS: This phenomenon occurred despite using several different batches of the 3-0 Supramid stent suture and the device had to be removed and replaced with another device without complication. In vitro microfluidic assessment of the device demonstrated no flow across the device tube despite over 150 mm Hg of pressure being exerted on the device. CONCLUSIONS: We hypothesize that the blockage occurred at the junction between the device tube and plate and that the ballooning phenomenon observed was due to a defect in the tube wall. This case highlights the importance of flow testing all glaucoma drainage devices before insertion given the variation in manufacturing conditions to avoid the risk of intraoperative complications.

Genotype-Phenotype Associations of IL6 and PRG4 With Conjunctival Fibrosis After Glaucoma Surgery.

Importance: Postsurgical fibrosis is a critical determinant of the long-term success of glaucoma surgery, but no reliable biomarkers are currently available to stratify the risk of scarring. Objective: To compare the clinical phenotype of patients with conjunctival fibrosis after glaucoma surgery with candidate gene expression tissue biomarkers of fibrosis. Design, Setting, and Participants: In this cross-sectional study, 42 patients were recruited at the time of glaucoma surgery at the Moorfields Eye Hospital from September 1, 2014, to September 1, 2016. The participants were divided into those with fibrosis and those without fibrosis. Main Outcomes and Measures: Genotype-phenotype correlations of the IL6 or PRG4 gene and detailed clinical phenotype. The IL6 and PRG4 protein expression in conjunctival tissues was also assessed using in situ immunohistochemical analysis. Central bleb area, maximal bleb area, and bleb height were graded on a scale of 1 to 5 (1 indicating 0%; 2, 25%; 3, 50%; 4, 75%; and 5, 100%). Bleb vascularity was graded on a scale of 1 to 5 (1 indicating avascularity; 2, normal; 3, mild; 4, moderate; and 5, severe hyperemia). Results: A total of 42 patients were recruited during the study period; 28 participants (67%) had previously undergone glaucoma surgery (fibrotic group) (mean [SD] age, 43.8 [3.6 years]; 16 [57%] female; 22 [79%] white), and 14 participants (33%) had not previously undergone glaucoma surgery (nonfibrotic group) (mean [SD] age, 47.7 [6.9] years; 4 [29%] female; 9 [64%] white). The fibrotic group had marked bleb scarring and vascularization and worse logMAR visual acuity. The mean (SD) grades were 1.4 (0.1) for central bleb area, 1.4 (0.1) for bleb height, and 3.4 (0.2) for bleb vascularity. The IL6 gene was upregulated in fibrotic cell lines (mean, 0.040) compared with nonfibrotic cell lines (mean, 0.011) (difference, 0.029; 95% CI, 0.015-0.043; P = .003). The PRG4 gene was also downregulated in fibrotic cell lines (0.002) compared with nonfibrotic cell lines (mean, 0.109; difference, 0.107; 95% CI, 0.104-0.110; P = .03). The study found a strong correlation between the IL6 gene and the number of glaucoma operations (r = 0.94, P < .001) and logMAR visual acuity (r = 0.64, P = .03). A moderate correlation was found between the PRG4 gene and the number of glaucoma operations (r = -0.72, P = .005) and logMAR visual acuity (r = -0.62, P = .03). Conclusions and Relevance: IL6 and PRG4 represent potential novel tissue biomarkers of disease severity and prognosis in conjunctival fibrosis after glaucoma surgery. Future longitudinal studies with multiple postoperative measures are needed to validate the effect of these potential biomarkers of fibrosis.

Local delivery of novel MRTF/SRF inhibitors prevents scar tissue formation in a preclinical model of fibrosis.

The myocardin-related transcription factor/serum response factor (MRTF/SRF) pathway represents a promising therapeutic target to prevent fibrosis. We have tested the effects of new pharmacological inhibitors of MRTF/SRF signalling in a preclinical model of fibrosis. CCG-222740, a novel MRTF/SRF inhibitor, markedly decreased SRF reporter gene activity and showed a greater inhibitory effect on MRTF/SRF target genes than the previously described MRTF-A inhibitor CCG-203971. CCG-222740 was also five times more potent, with an IC50 of 5 µM, in a fibroblast-mediated collagen contraction assay, was less cytotoxic, and a more potent inhibitor of alpha-smooth muscle actin protein expression than CCG-203971. Local delivery of CCG-222740 and CCG-203971 in a validated and clinically relevant rabbit model of scar tissue formation after glaucoma filtration surgery increased the long-term success of the surgery by 67% (P < 0.0005) and 33% (P < 0.01), respectively, and significantly decreased fibrosis and scarring histologically. Unlike mitomycin-C, neither CCG-222740 nor CCG-203971 caused any detectable epithelial toxicity or systemic side effects with very low drug levels measured in the aqueous, vitreous, and serum. We conclude that inhibitors of MRTF/SRF-regulated gene transcription such as CCG-222740, potentially represent a new therapeutic strategy to prevent scar tissue formation in the eye and other tissues.

Severe adverse events associated with local anaesthesia in cataract surgery: 1†year national survey of practice and complications in the UK.

BACKGROUND: Recent years have seen a major change in practice of local anaesthesia (LA) for cataract surgery. AIMS: (1) To estimate current usage of LA techniques for cataract surgery, (2) to estimate the incidence of severe adverse events associated with each LA technique, (3) to compare with our previous 2003 study. METHODS: This was a prospective, observational study of routine practice. For 13 months in 2012-2013, the British Ophthalmological Surveillance Unit sent monthly mailings to all senior British ophthalmologists, asking for reports of 'potentially sight-threatening or life-threatening complications of LA for cataract surgery'. Current practice was assessed by questionnaire. RESULTS: Cataract surgery comprised 3.4% general anaesthesia, 92.5% LA alone and 4.1% LA with sedation. Techniques for the estimated 357 000 LA cataracts were: 8.8% peribulbar, 1.3% retrobulbar, 50.5% sub-Tenon's, 1.4% subconjunctival, 13.8% topical, 24.2% topical-intracameral LA. Severe sight-threatening complications included seven globe perforations, one cilioretinal artery occlusion and one severe corneal oedema. Severe life-threatening complications included one profound vasovagal episode, one silent myocardial infarction, one anaphylactic reaction and one supraventricular tachycardia. Under-reporting means that more complications probably occurred. CONCLUSIONS: There has been a large swing towards 'non-injection' LA in recent years. Serious adverse events were reported with all techniques except topical-intracameral and subconjunctival LA, though the incidence appears lower for 'non-injection' LA.

Macular grid laser photocoagulation for branch retinal vein occlusion.

BACKGROUND: Branch retinal vein occlusion (BRVO) is the second most common cause of retinal vascular abnormality after diabetic retinopathy. Persistent macular oedema develops in 60% of eyes with a BRVO. Untreated, only 14% of eyes with chronic macular oedema will have a visual acuity (VA) of 20/40 or better. Macular grid laser photocoagulation is used for chronic non-ischaemic macular oedema following BRVO and has been the mainstay of treatment for over 20 years. New treatments are available and a systematic review is necessary to ensure that the most up-to-date evidence is considered objectively. OBJECTIVES: To examine the effects of macular grid laser photocoagulation in the treatment of macular oedema following BRVO. SEARCH METHODS: We searched CENTRAL, Ovid MEDLINE, EMBASE, Web of Science Conference Proceedings Citation Index, the metaRegister of Controlled Trials (mRCT), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 21 August 2014. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing macular grid laser photocoagulation treatment to another treatment, sham treatment or no treatment. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included five studies conducted in Europe and North America. Four separate trials compared grid laser to no treatment, sham treatment, intravitreal bevacizumab and intravitreal triamcinolone. One further trial compared subthreshold to threshold laser. Two of these trials were judged to be at high risk of bias in one or more domains.In one trial of grid laser versus observation, people receiving grid laser were more likely to gain visual acuity (VA) (10 or more ETDRS letters) at 36 months (RR 1.75, 95% confidence interval (CI) 1.08 to 2.84, 78 participants, moderate-quality evidence). The effect of grid laser on loss of VA (10 or more letters) was uncertain as the results were imprecise (RR 0.68, 95% CI 0.23 to 2.04, 78 participants, moderate-quality evidence). On average, people receiving grid laser had better improvement in VA (mean difference (MD) 0.11 logMAR, 95% CI 0.05 to 0.17, high-quality evidence). In a trial of early and delayed grid laser treatment versus sham laser (n = 108, data available for 99 participants), no participant gained or lost VA (15 or more ETDRS letters). At 12 months, there was no evidence for a difference in change in VA (from baseline) between early grid laser and sham laser (MD -0.03 logMAR, 95% confidence interval (CI) -0.07 to 0.01, 68 participants, low-quality evidence) or between delayed grid laser and sham laser (MD 0.00, 95% CI -0.04 to 0.04, 66 participants, low-quality evidence).The relative effects of subthreshold and threshold laser were uncertain. In one trial, the RR for gain of VA (15 or more letters) at 12 months was 1.68 (95% CI 0.57 to 4.95, 36 participants, moderate-quality evidence); the RR for loss of VA (15 or more letters) was 0.56 (95% CI 0.06 to 5.63, moderate-quality evidence); and at 24 months the change in VA from baseline was MD 0.07 (95% CI -0.10 to 0.24, moderate-quality evidence).The relative effects of macular grid laser and intravitreal bevacizumab were uncertain. In one trial, the RR for gain of 15 or more letters at 12 months was 0.67 (95% CI 0.39 to 1.14, 30 participants, low-quality evidence). Loss of 15 or more letters was not reported. Change in VA at 12 months was MD 0.11 logMAR (95% CI -0.36 to 0.14, low-quality evidence).The relative effects of grid laser and 1mg triamcinolone were uncertain at 12 months. RR for gain of VA (15 or more letters) was 1.13 (95% CI 0.75 to 1.71, 1 RCT, 242 participants, moderate-quality evidence); RR for loss of VA (15 or more letters) was 1.20 (95% CI 0.63 to 2.27, moderate-quality evidence); MD for change in VA was -0.03 letters (95% CI -0.12 to 0.06, moderate-quality evidence). Similar results were seen for the comparison with 4mg triamcinolone. Beyond 12 months, the visual outcomes were in favour of grid laser at 24 months and 36 months with people in the macular grid group gaining more VA.Four studies reported on adverse effects. Laser photocoagulation appeared to be well tolerated in the studies. One participant (out of 71) suffered a perforation of Bruch's membrane, but this did not affect visual acuity. AUTHORS' CONCLUSIONS: Moderate-quality evidence from one RCT supports the use of grid laser photocoagulation to treat macular oedema following BRVO. There was insufficient evidence to support the use of early grid laser or subthreshold laser. There was insufficient evidence to show a benefit of intravitreal triamcinolone or anti-vascular endothelial growth factor (VEGF) over macular grid laser photocoagulation in BRVO. With recent interest in the use of intravitreal anti-VEGF or steroid therapy, assessment of treatment efficacy (change in visual acuity and foveal or central macular thickness using optical coherence tomography (OCT)) and the number of treatments needed for maintenance and long-term safety will be important for future studies.

A rapidly growing lid lump.

A 97-year-old woman presented with a 5-month history of a rapidly growing, painless, left upper eyelid lesion. Examination revealed a large vascularised, ulcerated nodule on the left upper lid, causing significant ptosis. Wide local excision of the lesion was performed and the wound was left to heal by secondary intention. Histology and immunohistochemistry of the lesion confirmed a diagnosis of Merkel cell carcinoma, a rare primary malignancy of the eyelid which has significant morbidity and mortality. Although uncommon, this diagnosis should always be considered in any patient with a rapidly growing lid lump. In view of the patient's age, known dementia and family wishes, the patient was managed conservatively, with no further investigations performed. She was due to be followed up in clinic on a regular basis, but has since died from other causes.

Optical functional performance of the osteo-odonto-keratoprosthesis.

PURPOSE: The aim of this study was to evaluate optical and visual functional performance of the osteo-odonto-keratoprosthesis (OOKP). METHODS: Optical design and analysis was performed with customized optical design software. Nine patients with implanted OOKP devices and 9 age-matched control patients were assessed. Contrast sensitivity was assessed and glare effect was measured with a brightness acuity test. All OOKP patients underwent kinetic Goldmann perimetry and wavefront aberrometry and completed the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). RESULTS: Optical analysis showed that the optical cylinder is near diffraction-limited. A reduction in median visual acuity (VA) with increasing glare settings was observed from 0.04 logMAR (without glare) to 0.20 logMAR (with glare at "high" setting) and significantly reduced statistically when compared with the control group at all levels of glare (P < 0.05). Contrast sensitivity was significantly reduced when compared with age-matched controls at medium and high spatial frequencies (P < 0.05). Median Goldmann perimetry was 65 degrees (interquartile range, 64-74 degrees; V-4e isopters) and 69 degrees excluding 2 glaucomatous subjects. Several vision-related NEI VFQ-25 subscales correlated significantly with VA at various brightness acuity test levels and contrast sensitivity at medium spatial frequencies, including dependency, general vision, near activities and distance activities. CONCLUSIONS: The OOKP optical cylinder provides patients with a good level of VA that is significantly reduced by glare. We have shown in vivo that updates to the optical cylinder design have improved the patient's field of view. Reduction of glare and refinement of cylinder alignment methods may further improve visual function and patient satisfaction.

Electrooculogram (EOG) findings in a case of acute exudative polymorphous vitelliform maculopathy (AEPVM) detected following trauma.

PURPOSE: The purpose of this study was to monitor a case of acute exudative polymorphous vitelliform maculopathy detected following trauma. METHODS: Clinical examination included fundus photographs, optical coherence tomography (OCT) and fluorescein angiography. Pattern and full-field electroretinograms (PERG; ERG) and serial electrooculograms (EOG) were performed, incorporating the international standards. RESULTS: A 45-year-old Caucasian woman developed blurring of vision in both eyes 5 days after a serious road traffic accident. On examination, bilateral serous macular detachments and multiple small yellow subretinal lesions were observed in both eyes associated with areas of serous retinal detachment superior and inferior to the yellow lesions in the left eye. OCT showed retinal elevation with a band of high reflectance on the outer retina but no intra-retinal fluid or elevation of the retinal pigment epithelium (RPE). There was bilateral EOG reduction in keeping with generalised RPE dysfunction and pattern ERG evidence of left macular involvement. After 9 months, the patient reported spontaneous improvement in vision with gravitational settling and coalescence of the subretinal yellow deposits. At 37 months, there was improvement in the EOG and visual acuity. CONCLUSIONS: A rare case of AEPVM is described that was detected following trauma and which gradually improved over 37 months. The EOG showed evidence of generalised RPE dysfunction that resolved and may be useful in the monitoring of AEPVM.

Patient-reported benefit from botulinum toxin treatment for essential blepharospasm: using 2 assessment scales.

PURPOSE: To assess and compare the change in quality-of-life and function following treatment with botulinum toxin (BTX) using the Glasgow Benefit Inventory (GBI) and Blepharospasm Disability Index (BSDI) scores. METHODS: A cross-sectional study of 62 consecutive patients treated with BTX for blepharospasm conducted during a postinterventional telephone interview. Post hoc analysis converts the GBI to a score from -100 (maximum harm) through 0 (no effect) to +100 (maximum benefit). The BSDI is converted to a score on a scale from -4 (maximum harm) through 0 (no effect) to +4 (maximum benefit). A Wilcoxon signed-rank test and linear regression analysis were performed. RESULTS: A statistically significant benefit (Wilcoxon signed-rank test) from treatment of 31.36 (95% confidence interval = 26.22-36.50; p < 0.001) and 1.04 (95% confidence interval = 0.80-1.27; p < 0.001) using the GBI and BSDI scores, respectively. Regression analysis was performed demonstrating a strong positive correlation between both scales (r = 0.637). CONCLUSIONS: BTX treatment for blepharospasm is associated with significant patient-reported improvements in quality-of-life (GBI) and functional ability (BSDI) with a strong positive correlation between both scores.

Posterior capsule rupture rate with akinetic and kinetic block anesthetic techniques.

A systematic literature search was performed to identify prospective randomized studies comparing akinetic (sub-Tenon, peribulbar, or retrobulbar) and kinetic (topical or topical and intracameral) local anesthesia for phacoemulsification surgery. Only studies that stated the rate of posterior capsule rupture or that stated without qualification that there were no intraoperative complications were included. Of the initial 3182 articles, 15 papers met the inclusion criteria. The number of eyes ranged between 26 and 282 per group (mean 95.4 eyes per group), with a total of 2862 eyes. Eleven articles mentioned posterior capsule rupture specifically; 4 stated that no intraoperative complications occurred. Eleven (0.74%) of 1494 eyes in the akinetic group and 11 (0.80%) of 1368 eyes in the kinetic group experienced posterior capsule rupture. The chi-square test confirmed the difference was not statistically significant (P = .84). This analysis indicates that there appears to be no clinically or statistically significant difference in the risk for posterior capsule rupture between akinetic and kinetic local anesthesia techniques.

Black-on-clear piggyback technique for a black occlusive intraocular device in intractable diplopia.

Black occlusive intraocular devices have been used successfully for intractable binocular diplopia. We describe a novel technique of implanting both a black occlusive device and a clear poly(methyl methacrylate) intraocular lens (IOL) in the capsular bag during phacoemulsification surgery. If the need should arise at a later date, this approach will allow safer and easier explantation of the black occlusive device, avoiding the need for IOL exchange.

Reversible mental status change and renal dysfunction associated with the use of high-dose oral valaciclovir therapy for acute retinal necrosis.

PURPOSE: The purpose of this study was to report the case of a patient with acute retinal necrosis who developed neurotoxicity while being treated with oral valaciclovir antiviral therapy. METHODS: Testing used was clinical examination including fundus photographs, renal biochemistry, cerebrospinal fluid analysis, and renal ultrasound. RESULTS: A 63-year-old, healthy, white woman was being treated with oral valaciclovir for acute retinal necrosis. Several days later, she developed visual hallucinations and confusion. Renal biochemistry was abnormal, and renal ultrasound was normal. Cerebrospinal fluid cellularity was normal, but cerebrospinal fluid 9-carboxymethoxymethylguanine, an aciclovir metabolite, level was elevated. Treatment was changed to intravenous aciclovir titrated based on serum aciclovir levels with intravenous fluid supplementation to good effect. CONCLUSION: Regular monitoring of renal function and ample fluid intake are important when high doses of aciclovir/valaciclovir are used, even in patients with no previous history of renal failure. Monitoring of serum aciclovir level is useful in those with renal impairment to titrate doses, and high-dose oral valaciclovir should be used with caution.

Face-to-face upright seated positioning for cataract surgery in patients who cannot lie flat.

We describe a technique for cataract surgery in patients unable to adopt the conventional face-to-ceiling position. A standard reclining operating chair and operating microscope are used. Patients are seated instead of lying down, with the chair back elevated 30 to 80 degrees above the horizontal and the operating microscope rotated 45 to 60 degrees to vertical. The surgeon is seated or standing, facing the patient. A clear corneal incision is used via an inferior, temporal, or inferotemporal approach under topical intracameral anesthesia without sedation. Results of this technique in a case series comprising 32 eyes are reported. The technique is useful for patients unable to adopt the traditional approach for cataract surgery and at high risk for complications from general anesthesia. It is technically challenging so should be attempted by experienced surgeons only.