Combined aqueous misdirection and persistent choroidal effusions following implantation of a Preserflo MicroShunt.

AIM: To describe a case of aqueous misdirection complicated by subsequent persistent choroidal effusions following implantation of a Preserflo MicroShunt (PMS) device to treat advanced closed angle glaucoma. METHODS: A 67-year-old caucasian female with advanced primary angle-closure glaucoma on four medications with an intraocular pressure (IOP) of 26 mm Hg was listed for a PMS insertion with mitomycin C (MMC). RESULTS: Past ocular history was significant for pseudophakia and previous yttrium aluminum garnet (YAG) peripheral iridotomy. Surgery was uneventful but on the first postoperative day, she developed aqueous misdirection complicated by subsequent development of persistent uveal effusions. Conventional treatment strategies including atropine drops, YAG hyaloidotomy and choroidal effusion drainage proved ineffective. A combination of oral steroids and pars plana vitrectomy (PPV) along with an irido-zonulo-hyloidectomy (IZH) proved efficacious. CONCLUSION: To the best of the author's knowledge, this is the first published case of aqueous misdirection complicated with the presence of significant, unresolving choroidal effusions, highlighting the possibility and sequelae of comorbid pathology in nanophthalmic eyes.

One-year surgical outcomes of the PreserFlo MicroShunt in glaucoma: a multicentre analysis.

BACKGROUND/AIMS: To evaluate the efficacy and safety of the PreserFlo MicroShunt glaucoma device in a multicentre cohort study. METHODS: All consecutive patients who received the microshunt with mitomycin-C (MMC) 0.4 mg/mL from May 2019 to September 2020 in three UK tertiary centres. Primary outcome at 1 year was a complete success, with failure defined as intraocular pressure (IOP) >21 mmHg or <20% reduction, IOP≤5 mmHg with any decreased vision on two consecutive visits, reoperation or loss of light perception vision. Secondary outcomes were IOP, best-corrected visual acuity, medications, complications, interventions and reoperations. We also performed subgroup analyses for severe glaucoma and assessed risk factors for failure. RESULTS: 104 eyes had 1-year follow-up. Complete and qualified success at 1 year were achieved in 51.9% (N=54) and 16.4% (N=17), respectively, and failure occurred in 31.7% (N=33). There was a significant reduction in IOP (mmHg) from preoperatively (23.4±0.8, N=104) to 12 months (14.7±0.6, N=104) (p<0.0001). Antiglaucoma medications also decreased from preoperatively (3.4±0.1, N=104) to 12 months (0.7±0.1, N=104) (p<0.0001). Multivariate analyses showed an association between higher mean deviation and failure (HR 1.055, 95% CI 1.0075 to 1.11, p=0.0227). Complications were hypotony (19.2%; N=20), choroidal detachments (10.6%; N=11), hyphaema (5.8%; N=6) and bleb leak (5.8%; N=6). Needling and 5-fluorouracil injections were performed in 12.5% (N=13) and 33.7% (N=35), respectively, and 11.5% (N=12) required revision surgery. CONCLUSION: The PreserFlo MicroShunt with MMC 0.4 mg/mL showed an overall success rate of 68.3% at 1 year, and led to significant IOP and medication reduction with a low rate of adverse effects.

Insertion of a Preserflo microshunt inside a non-valved glaucoma shunt to treat late-onset hypotony.

We present a case of advanced glaucoma with previously failed trabeculectomy who underwent a Baerveldt tube (BVT) insertion, with initial success. However, 9 months post BVT insertion he developed profound clinically significant hypotony. Two attempts at controlling this with suture exchange led to episodes of significant ocular hypertension, followed by hypotony each time. We describe a technique of using a cut segment of the novel, polystyrene-block-isobutylene-block- styrene (SIBs) based Preserflo Microshunt (Santen Inc., Miami, FL) inserted into the tip of a BVT to control late onset hypotony with success. IOP at 6 weeks was 12mmHg on two drops with complete resolution of the choroidal maculopathy.

Minimally Invasive Glaucoma Surgical Techniques for Open-Angle Glaucoma: An Overview of Cochrane Systematic Reviews and Network Meta-analysis.

IMPORTANCE: Glaucoma affects more than 75 million people worldwide. Intraocular pressure (IOP)-lowering surgery is an important treatment for this disease. Interest in reducing surgical morbidity has led to the introduction of minimally invasive glaucoma surgeries (MIGS). Understanding the comparative effectiveness and safety of MIGS is necessary for clinicians and patients. OBJECTIVE: To summarize data from randomized clinical trials of MIGS for open-angle glaucoma, which were evaluated in a suite of Cochrane reviews. DATA SOURCES: The Cochrane Database of Systematic Reviews including studies published before June 1, 2021. STUDY SELECTION: Reviews of randomized clinical trials comparing MIGS with cataract extraction alone, other MIGS, traditional glaucoma surgery, laser trabeculoplasty, or medical therapy. DATA EXTRACTION AND SYNTHESIS: Data were extracted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines by one investigator and confirmed by a second. Methodologic rigor was assessed using the AMSTAR 2 appraisal tool and random-effects network meta-analyses were conducted. MAIN OUTCOMES AND MEASURES: The proportion of participants who did not need to use medication to reduce intraocular pressure (IOP) postsurgery (drop-free). Outcomes were analyzed at short-term (<6 months), medium-term (6-18 months), and long-term (>18 months) follow-up. RESULTS: Six eligible Cochrane reviews were identified discussing trabecular bypass with iStent or Hydrus microstents, ab interno trabeculotomy with Trabectome, subconjunctival and supraciliary drainage devices, and endoscopic cyclophotocoagulation. Moderate certainty evidence indicated that adding a Hydrus safely improved the likelihood of drop-free glaucoma control at medium-term (relative risk [RR], 1.6; 95% CI, 1.4 to 1.8) and long-term (RR, 1.6; 95% CI, 1.4 to 1.9) follow-up and conferred 2.0-mm Hg (95% CI, -2.7 to -1.3 mm Hg) greater IOP reduction at long-term follow-up, compared with cataract surgery alone. Adding an iStent also safely improved drop-free disease control compared with cataract surgery alone (RR, 1.4; 95% CI, 1.2 to 1.6), but the short-term IOP-lowering effect of the iStent was not sustained. Addition of a CyPass microstent improved drop-free glaucoma control compared with cataract surgery alone (RR, 1.3; 95% CI, 1.1 to 1.5) but was associated with an increased risk of vraision loss. Network meta-analyses supported the direction and magnitude of these results. CONCLUSIONS AND RELEVANCE: Based on data synthesized in Cochrane reviews, some MIGS may afford patients with glaucoma greater drop-free disease control than cataract surgery alone. Among the products currently available, randomized clinical trial data associate the Hydrus with greater drop-free glaucoma control and IOP lowering than the iStent; however, these effect sizes were small.

Agreement amongst consultant ophthalmologists on levels of visual disability required for eligibility for certificate of sight impairment : Sight impairment registration using binocular composite visual fields.

BACKGROUND: Registration as sight impaired allows access to services important for patients. The rates of sight impairment due to visual field loss are underestimated. Previous work has shown that evaluation of visual field defects in both eyes produces poor agreement among ophthalmologists for categorisation of patients as eligible for sight impairment registration. AIM: To evaluate the impact of binocular summation of both eye glaucomatous visual field defects on agreement for sight impairment registration. METHODS: Thirty consultant ophthalmologists (Graders), graded 50 glaucomatous visual field sets. Each consisted of both monocular fields and summated binocular plots. Graders classified the visual field sets as sight impaired (SI), severely sight impaired (SSI) or neither. Trichotomous, (SI, SSI or no sight impairment) and dichotomous (any sight impairment versus no sight impairment) concordance values were estimated for the group of graders as a whole and for glaucoma and non-glaucoma experts. RESULTS: For trichotomous analysis the overall kappa agreement rate was 0.29; for dichotomous analysis it was 0.40. There was no material difference between glaucoma experts and non-experts. CONCLUSION: Overall agreement was modest. Grading for SI showed the poorest levels of agreement. Using binocular fields does not appear to improve concordance for sight impairment registration. Moreover, there is no difference in agreement between glaucoma and non-glaucoma experts. An overall score for visual disability using mean deviation may be a more pragmatic approach.

Gonioscopy-assisted Transluminal Trabeculotomy in Uveitic Glaucoma Secondary to Juvenile Idiopathic Arthritis.

Gonioscopy-assisted transluminal trabeculotomy (GATT) is a minimally invasive ab interno procedure, performed with guidance of an illuminating microcatheter device (iTrack). The pathophysiology of raised intraocular pressure (IOP) in uveitic glaucoma is commonly due to increased resistance at the trabecular meshwork-Schlemm canal. By removing this resistance, GATT can potentially control the IOP. In addition, the ab interno approach avoids violating the conjunctiva and reduces the risk of complications including infection, leak, and hypotony. In this series, we discuss 3 uveitic glaucoma cases secondary to juvenile idiopathic arthritis (JIA) that underwent GATT. Case 1 was a 16-year-old phakic female with a preoperative IOP of 25 to 33 mm Hg had 360-degree GATT; her IOP remained stable at 6 to 10 mm Hg over 14 months. Case 2 was a 23-year-old pseudophakic female with a preoperative IOP of 28 to 34 mm Hg had 180-degree GATT; her IOP reduced to 8 mm Hg over 10 months. Case 3 was an 8-year-old aphakic male with a preoperative IOP of 21 to 32 mm Hg had 360-degree GATT; his IOP remained stable at 13 to 15 mm Hg over 21 months. In our limited case series, GATT is very successful in controlling IOP in young uveitic patients with JIA by surgically targeting the underlying pathophysiology.

Strong vaccine responses during chemotherapy are associated with prolonged cancer survival.

Therapeutic cancer vaccines have effectively induced durable regressions of premalignant oncogenic human papilloma virus type 16 (HPV16)-induced anogenital lesions. However, the treatment of HPV16-induced cancers requires appropriate countermeasures to overcome cancer-induced immune suppression. We previously showed that standard-of-care carboplatin/paclitaxel chemotherapy can reduce abnormally high numbers of immunosuppressive myeloid cells in patients, allowing the development of much stronger therapeutic HPV16 vaccine (ISA101)-induced tumor immunity. We now show the clinical effects of ISA101 vaccination during chemotherapy in 77 patients with advanced, recurrent, or metastatic cervical cancer in a dose assessment study of ISA101. Tumor regressions were observed in 43% of 72 evaluable patients. The depletion of myeloid suppressive cells by carboplatin/paclitaxel was associated with detection of low frequency of spontaneous HPV16-specific immunity in 21 of 62 tested patients. Patients mounted type 1 T cell responses to the vaccine across all doses. The group of patients with higher than median vaccine-induced immune responses lived longer, with a flat tail on the survival curve. This demonstrates that chemoimmunotherapy can be exploited to the benefit of patients with advanced cancer based on a defined mode of action.

Subconjunctival draining minimally-invasive glaucoma devices for medically uncontrolled glaucoma.

BACKGROUND: Glaucoma is a leading cause of irreversible blindness. Subconjunctival draining minimally-invasive glaucoma devices such as the Xen gelatin implant and InnFocus stent have been introduced as a treatment to prevent glaucoma progressing.These implants provide a channel to allow aqueous humour from the anterior chamber of the eye to drain into the subconjunctival space on the surface of the eye thus reducing intraocular pressure (IOP) and mimicking the mechanism of the most commonly undertaken glaucoma surgery, trabeculectomy. OBJECTIVES: To evaluate the efficacy and safety of subconjunctival draining minimally-invasive glaucoma devices in treating people with open angle glaucoma and ocular hypertension whose condition is inadequately controlled with drops. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2018, Issue 6); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 10 July 2018. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) of Xen gelatin implant or InnFocus MicroShunt to other surgical treatments (other minimally-invasive glaucoma device techniques, trabeculectomy), laser treatment or medical treatment. We also planned to include trials where these devices were combined with phacoemulsification compared to phacoemulsification alone. DATA COLLECTION AND ANALYSIS: We planned to have two review authors independently extract data from reports of included studies using a data collection form and analyse data based on methods expected by Cochrane. Our primary outcome was mean change in IOP. Secondary outcomes included proportion of participants who were drop-free; proportion of participants who achieved an IOP of 21 mmHg or less, 17 mmHg or less or 14 mmHg or less; and proportion of participants experiencing intra- and postoperative complications. We planned to measure all outcomes in the short-term (six to 18 months), medium-term (18 to 36 months), and long-term (36 months onwards). MAIN RESULTS: We found no completed RCTs that met our inclusion criteria. We found one ongoing study (NCT01881425). The study compares InnFocus MicroShunt to trabeculectomy in people with primary open angle glaucoma. The primary outcome is greater than 20% IOP reduction from baseline to 12 months' follow-up. A total of 889 people aged between 40 and 85 years have been enrolled. The estimated study completion date is November 2019. AUTHORS' CONCLUSIONS: There is currently no high-quality evidence for the effects of subconjunctival draining minimally-invasive glaucoma devices for medically uncontrolled open angle glaucoma. Properly designed RCTs are needed to assess the medium- and long-term efficacy and safety of this technique.

Evaluating the Variation of Intraocular Pressure With Positional Change During Colorectal Laparoscopic Surgery: Observational Study.

BACKGROUND: The incidence of perioperative visual loss following colorectal surgery in the US is quoted as 1.24 per 10,000. Raised intraocular pressure (IOP) during extreme Trendelenburg position leading to reduced optic nerve perfusion is thought to be a cause. OBJECTIVE: To assess the effect of the degree of Trendelenburg tilt and time spent in Trendelenburg on IOP during laparoscopic colorectal surgery. METHODS: Fifty patients undergoing laparoscopic colorectal surgery were recruited. A Tonopen XL applanation tonometer was used to take IOP measurements hourly during surgery, and each time the operating table was tilted. A correlation coefficient for the degree of Trendelenburg tilt and IOP was calculated for each patient. Group 1 included patients undergoing a right-sided colonic procedure, and Group 2 included all left-sided colonic operations. RESULTS: The mean age of Group 1 participants (n=25) was 69 years (SD 14), and Group 2 (n=25) was 63 years (SD 16; P>.05). The average length of surgery for Group 1 was 142 minutes (SD 48), and Group 2 was 268 minutes (SD 99; P≤.05). The mean maximum degree of Trendelenburg tilt in Group 1 was 10 (SD 7) and Group 2 was 19 (SD 6; P≤.05). The mean IOP increase was 9 mm Hg (SD 5) for Group 1 and 15 mm Hg (SD 5) in Group 2 (P≤.05). An overall correlation coefficient for the degree of Trendelenburg tilt and IOP change (n=48) was .78. CONCLUSIONS: There is a strong correlation between IOP elevation during laparoscopic colorectal surgery and the degree of Trendelenburg tilt. This may be significant for patients undergoing prolonged surgery and especially those with glaucoma.

Can the SENSIMED Triggerfish® lens data be used as an accurate measure of intraocular pressure?

PURPOSE: The SENSIMED Triggerfish® contact lens sensor (CLS) has an embedded micro-sensor that captures spontaneous circumferential changes at the corneoscleral junction and transmits them via an antenna to a device where these measurements are stored. During laparoscopic colorectal surgery, patients are placed in Trendelenburg position which has been shown to increase intraocular pressure (IOP). Laparoscopic colorectal surgery requires both pneumoperitoneum and Trendelenburg positioning; therefore, IOP can vary significantly. We aimed to assess whether circumferential changes in the corneoscleral area can be correlated to IOP changes measured using Tono-pen® XL applanation tonometer during laparoscopic colorectal surgery. METHOD: Patients undergoing laparoscopic colorectal resections were included. On the day of surgery, baseline IOP was taken and the SENSIMED Triggerfish® CLS was then set up in one eye of the patient. During surgery (whilst under general anaesthetic), IOP measurements were taken in the contralateral eye using a Tono-pen® XL applanation tonometer every hour and any time the table was moved to record the fluctuations of IOP during surgery and any association with position change. The timings of these readings were documented. RESULTS: Twenty patients were included in this study (six males, 14 females). Average age was 64.6 years (SD = 16.3). The fluctuation in IOP measured in the reference eye ranged between 6.3 and 46.7 mmHg. The mean correlation coefficient between CLS output measurements and these IOP measurements was r = 0.291 (95% CI). CONCLUSION: Our results showed a weak correlation between the SENSIMED Triggerfish® CLS data output and IOP measurements taken using the Tono-pen® XL applanation tonometer.

Short-term effect of diode laser cyclophotocoagulation on intraocular pressure: a prospective study.

BACKGROUND: This aims to determine the immediate and short-term risk of intraocular pressure spikes following diode laser cyclophotocoagulation. DESIGN: This study is a prospective, consecutive cohort study in a UK teaching hospital. PARTICIPANTS: Fifty-three consecutive patients undergoing cyclophotocoagulation were invited to participate in this study. METHODS: Intraocular pressure (IOP) measurements were taken immediately prior to cyclodiode laser, hourly for the first 3 h after laser, on the first and seventh postoperative days, and at three months following laser. MAIN OUTCOME MEASURES: Eyes experiencing intraocular pressure elevation defined at two levels (≥3 mm Hg and ≥10 mm Hg from the pretreatment level) were identified. RESULTS: Seventeen eyes (34%) had an elevation in intraocular pressure (≥3 mmHg) during the first 3 h postoperatively with a mean increase of 10.3 mmHg. No preoperative or perioperative associations were found for a postcyclodiode spike within the first 3 postoperative hours.No association was found between pressure spikes and visual acuity, reduction of glaucoma medication or final postoperative intraocular pressure at 3 months. Eyes that did not have an IOP spike during the first 3 h postoperatively had a greater reduction in IOP at 3 months (15.2 mmHg vs. 10.2 mmHg; P = 0.184). CONCLUSION: IOP spikes are common in the immediate period after cyclophotocoagulation. An elevation in IOP is noted after the first hour in the vast majority who experience a spike in the first 3 h post-procedure.

Delayed presentation of melanoma-associated retinopathy and subsequent resolution with cytoreduction surgery.

BACKGROUND: To present a case of melanoma-associated retinopathy (MAR) which manifested 26 months prior to a formal diagnosis of melanoma. METHODS: Case report. RESULTS: A 72-year-old female presented with bilateral continuous photopsia consistent with MAR of 7-months duration. At this point, visual function appeared normal with the exception of mildly impaired colour vision (10/17 Ishihara plates). The flash electroretinographic (ERG) revealed extinguished rod responses, a normal a-wave and reduced b-wave (electronegative ERG) on the maximal combined response, absent oscillatory potentials and broadened a-wave trough on the cone response. Multifocal ERG (mfERG) responses were delayed and demonstrated atypical morphology. Nineteen months after the initial presentation, her visual symptoms had progressed significantly with constant debilitating photopsia in combination with 13 kg weight loss. Biopsy of a now evident left axillary mass demonstrated a metastatic high-grade malignant melanoma. No primary was detected, and an axillary lymph node clearance was undertaken. Subsequently, visual symptoms resolved with corresponding improvement in the ERG over the next 18 months. Rod responses recovered such that the amplitude was at the lower limit of normal and the mfERG response delay lessened. Unfortunately, the melanoma recurred and the patient passed away 6 months later. Visual symptoms did not recur. CONCLUSION: We present a case which demonstrates MAR may precede the formal diagnosis of melanoma by up to 26 months. The potential for improvement in the rod visual function persists over a period of years with normalisation of an electronegative waveform. In this case, cytoreductive surgery resulted in complete resolution of the MAR, which did not return even with a recurrence of the tumour.

Repeatability of ocular response analyzer metrics: a gender-based study.

PURPOSE: To assess the repeatability of Goldmann-correlated intraocular pressure (IOPG), corneal-compensated IOP (IOPCC), corneal hysteresis (CH), and the corneal resistance factor (CRF) obtained with the Ocular Response Analyzer (ORA) in normal eyes and to determine whether any differences in corneal biomechanical parameters or their repeatability exist between the sexes. METHODS: A prospective observational study assessing 100 normal adults (50 men and 50 women; median age, 54.5 years). Comparison of ORA parameters measured in both eyes in three sets of four consecutive readings by one examiner within a 30-minute period. RESULTS: The mean values of the ORA parameters assessed, the intraclass correlation coefficient (ICC) and the coefficient of repeatability (CR), were as follows for the right eye (n = 100): IOPG, 16.2 ± 3.3 mm Hg (ICC, 0.96; CR, 6.37); IOPCC, 16.2 ± 3.2 (ICC, 0.94; CR, 6.29); CRF, 10.9 ± 1.9 (ICC, 0.91; CR, 3.62); CH, 10.6 ± 1.7 (ICC, 0.94; CR, 3.37). The ICC between the readings was excellent (>0.9) for all the ORA parameters in both sexes, with the exception of one group (female CRF ICC, 0.86). Coefficient of repeatability of the instrument satisfies the British Standards Institution criteria for repeatability. There were no significant differences between corneal biomechanical factors and IOP results for men and women. CONCLUSIONS: Corneal biomechanical parameters measured by the ORA provide repeatable results in normal eyes, with no significant difference between the sexes.

Attitudes of consultant ophthalmologists in the UK to initial management of glaucoma patients presenting with severe visual field loss: a national survey.

BACKGROUND: Recent National Institute of Clinical Excellence guidance suggests primary surgery should be offered to patients presenting with glaucoma with severe visual field loss. We undertook a survey of UK consultant ophthalmologists to determine if this represents current practice and explore attitudes towards managing patients with advanced glaucoma at presentation. DESIGN: Questionnaire evaluation study. PARTICIPANTS: All consultant ophthalmologists currently practicing in the UK. METHODS: A single-page questionnaire was posted to all consultants (n = 910) currently practicing in the UK along with a pre-paid return envelope. A second questionnaire was sent to non-responders (n = 459). MAIN OUTCOME MEASURES: Questionnaire responses. RESULTS: 626 responses were received representing 68.8% of the population surveyed. 152 (24%) volunteered a specialist interest in glaucoma. Consensus opinion for both glaucoma specialists (64.9%) and non-glaucoma specialists (62.4%) was to start with primary medical therapy, most commonly citing surgical risk as the primary reason (23% and 22%, respectively) for this approach. Most felt the highest intraocular pressure measurement during follow up (measured in clinic) was the most important variable for prevention of further visual loss (60% of glaucoma specialists and 55% of non-glaucoma specialists). Eighty-three per cent of all responders suggested they would change their practice if evidence supporting primary surgery as a safe and more effective approach existed. CONCLUSIONS: Recent National Institute of Clinical Excellence guidance does not reflect the current management approach of UK ophthalmologists. The primary concern was related to potential complications of surgery although most practitioners would be willing to change their practice if evidence existed supporting primary surgery in patients presenting with advanced glaucoma.

Outcome of trabeculectomy with mitomycin C in patients with advanced glaucoma.

BACKGROUND/AIMS: To determine the medium-term intraocular pressure (IOP) control and visual outcomes for patients with advanced glaucoma undergoing trabeculectomy with mitomycin C. METHODS: All patients with advanced glaucoma (MD -20 dB or above) undergoing trabeculectomy with mitomycin C between 2000 and 2008 under the care of a single glaucoma surgeon were included. IOP, visual acuity and visual field outcomes were assessed from data prospectively collected into a surgical outcome database. RESULTS: 103 patients were eligible for inclusion. The post-trabeculectomy group mean IOP varied between 11.3 and 13.3 mm Hg between 1 and 7 years. At year 5, 85.2% had an IOP of <16 mm Hg, and 96.3% had an IOP of < 21 mm Hg. The number completing a reliable visual-field exam decreased significantly year on year, but the change in mean MD for the group as a whole and for individual patients remained stable. 28 patients experienced a significant reduction in acuity defined as two or more lines of Snellen, although this was not due to glaucoma surgery in the majority. The only preoperative determinant for a significant reduction in VA was the preoperative MD (-27.00 dB (n=21) compared with -24.79 dB (n=63; p=0.029)). CONCLUSION: Trabeculectomy is a successsful method of controlling IOP in the short to medium term in patients with advanced glaucoma.