Ophthalmology

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Improving the screening of risk factors in diabetic retinopathy
(Taylor and Francis Group, 2022-05) Scanlon, Peter; Scanlon, Peter; Medical and Dental
Introduction: In 2002, Diabetic Retinopathy was reported as the leading cause of blindness in the working age group. The introduction of systematic screening programs in the UK has reduced visual loss and blindness due to diabetic retinopathy, but it does still occur with catastrophic consequences for the individual. Areas covered: The author conducted an ongoing search for articles relating to diabetic retinopathy since 2000 utilizing Zetoc Alert with keywords and contents page lists from relevant journals. This review covers the risk factors for loss of vision due to diabetic retinopathy and discusses ways in which the awareness of these risk factors can be used to further reduce visual loss. Some risk factors such as glycemic and B/P control are well known from landmark trials. This review has included these factors but concentrated more on the evidence behind those risk factors that are not so clearly defined or so well known. Expert opinion: The major risk factors are well known, but one continues to find that people with diabetes lose vision in situations in which a better awareness of the risks by both the individual with diabetes and the health workers involved may have prevented the visual loss.
Anterior approach ptosis surgery: comparison of absorbable polyglactin sutures and non-absorbable polyester sutures. Does Vicryl stand the test of time?
(Taylor and Francis Group, 2021-08-01) Manasseh, Gemma; Hunt, Samantha; Garrott, Helen; Ford, Rebecca; Caesar, Richard; Harrad, Richard; Caesar, Richard; Medical and Dental
Purpose: To determine whether the long-term success of ptosis surgery is influenced by the use of absorbable or non-absorbable sutures to advance the levator aponeurosis onto the tarsal plate. Methods: Multi-centre retrospective comparative study of re-operation rates in primary anterior approach ptosis surgery using absorbable polyglactin sutures (Vicryl) and non-absorbable polyester sutures (Ethibond). The Medisoft audit tool was used to identify all patients who underwent primary ptosis surgery for aponeurotic ptosis, performed by five oculoplastic consultants within a 7-year period, across two NHS Ophthalmology departments. The electronic patient records were reviewed for each patient. Basic demographics, suture material, and post-operative complications were recorded. All patients requiring repeat surgery between the study dates and the present day were recorded, allowing a minimum postoperative period of 3 years and 10 months. Re-operation rates in surgery using absorbable Vicryl sutures and non-absorbable Ethibond sutures were compared using Fisher's exact test. Results: Four hundred and fifty-five operations in 330 patients were performed within the study period that met the inclusion and exclusion criteria. Fifty-seven percent of the patients were female, with an average age of 68.8 years. One hundred and sixty-nine operations in 128 patients were performed using absorbable Vicryl sutures. Of these, 22 (13.0%) required repeat operations. Two hundred and eighty-six operations in 202 patients were performed using non-absorbable Ethibond sutures. Of these, 17 (5.9%) required repeat operations. The two-tailed P-value was 0.0143. Conclusion: The use of non-absorbable Ethibond sutures to advance the levator aponeurosis onto the tarsal plate in primary ptosis surgery is associated with improved long-term success and reduced need for secondary surgery.
Ganglion Cell Complex: The Optimal Measure for Detection of Structural Progression in the Macula
(Elsevier, 2021-12-21) Mohammadzadeh, Vahid; Su, Erica; Rabiolo, Alessandro; Shi, Lynn; Zadeh, Sepideh; Law, Simon; Coleman, Anne; Caprioli, Joseph; Weiss, Robert; Nouri-Mahdavi, Kouros; Rabiolo, Alessandro; Medical and Dental
Purpose: To test the hypothesis that macular ganglion cell complex (GCC) thickness from optical coherence tomography (OCT) provides a stronger change signal regardless of glaucoma severity compared with other macular measures. Design: Prospective cohort study. Methods: Eyes were from 112 patients with moderate to severe glaucoma at baseline from a tertiary glaucoma center. In each 3° × 3° macular superpixel, a hierarchical Bayesian random intercept and slope model with random residual variance was fit to longitudinal full macular thickness (FMT), outer retina layers, GCC, ganglion cell-inner plexiform layer (GCIPL), and ganglion cell layer (GCL) measurements. We estimated population- and individual-level slopes and intercepts. Proportions of substantial worsening and improving superpixel slopes were compared between layers and in superpixels with mild to moderate vs severe damage (total deviation of corresponding visual field location ≥ -8 vs < -8 dB). Results: Mean (SD) follow-up time and baseline 10-2 visual field mean deviation were 3.6 (0.4) years and -8.9 (5.9) dB, respectively. FMT displayed the highest proportion of significant negative slopes (1932/3519 [54.9%]), followed by GCC (1286/3519 [36.5%]), outer retina layers (1254/3519 [35.6%]), (GCIPL) (1075/3518 [30.6%]), and (GCL) (698/3518 [19.8%]). Inner macular measures detected less worsening in the severe glaucoma group; yet GCC (223/985 [22.6%]) identified the highest proportion (GCIPL: 183/985 [18.6%]; GCL: 106/985 [10.8%]). Proportions of positive rates were small and comparable among all measures. Conclusions: GCC is the optimal macular measure for detection of structural change in eyes with moderate to severe glaucoma. Although a higher proportion of worsening superpixels was observed for FMT, a large portion of FMT change could be attributed to changes in outer retina layers.
Evaluation of standard of care intravitreal aflibercept treatment of diabetic macular oedema treatment-naive patients in the UK: DRAKO study 12-month outcomes
(Springer Nature, 2021-07-09) Sivaprasad, Sobha; Ghanchi, Faruque; Kelly, Simon; Kotagiri, Ajay; Talks, James; Scanlon, Peter; McGoey, Hellen; Nolan, Andrew; Saddiq, Moneeb; Napier, Jackie; Scanlon, Peter; Medical and Dental
Objectives: DRAKO (NCT02850263) is a 24-month, prospective, non-interventional, multi-centre cohort study which enroled patients diagnosed with centre-involving diabetic macular oedema (DMO). The study aims to evaluate standard of care with intravitreal aflibercept (IVT-AFL) treatment in the UK. This analysis describes the anti-vascular endothelial growth factor (anti-VEGF) treatment-naive patient cohort after 12-month follow-up. Methods: Study eyes were treated with IVT-AFL as per local standard of care. The mean change in best-corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline at 12 months were measured and stratified by baseline factors. The number of injections and safety data were also evaluated. Results: A total of 507 patients were enroled from 35 centres. Mean (SD) baseline BCVA was 71.4 (12.0) letters and CST was 448.7 (88.7) µm, with 63.1% of patients presenting with baseline BCVA ≥ 70 letters (mean 78.1). Mean (SD) change in BCVA of 2.5 (12.2) letters and CST of -119.1 (116.4) µm was observed at month 12. A 7.3 letter gain was observed in patients with baseline BCVA < 70 letters. Mean number (SD) of injections in year one was 6.4 (2.1). No significant adverse events were recorded. Conclusion: Year one results indicated that IVT-AFL was an effective treatment for DMO in standard of care UK clinical practice, maintaining or improving visual acuity in treatment-naive patients with good baseline visual acuity, despite some patients being undertreated versus the summary of product characteristics. These results also demonstrated the clinical importance and meaningful impact of diabetic retinopathy screening in the UK.
Comparison of preserved bimatoprost 0.01% with preservative-free tafluprost: A randomised, investigator-masked, 3-month crossover, multicentre trial, SPORT II
(SAGE Publications, 2021-04) Lemmens, Sophie; Rossetti, Luca; Oddone, Francesco; Sunaric-Mégevand, Gordana; Hommer, Anton; Vandewalle, Evelien; Cordeiro, Maria Francesca; McNaught, Andrew; Montesano, Giovanni; Stalmans, Ingeborg; McNaught, Andrew; Medical and Dental
Importance: This study compares the efficacy and tolerability of a preservative-free prostaglandin analogue (tafluprost 15 mg/ml) to a prostaglandin analogue that uses 0.02% of benzalkonium chloride (bimatoprost 0.1 mg/ml). Background: Different prostaglandin analogues have been commercially approved, with differences in tolerability. Design: Prospective, randomised, investigator-masked, 3-month crossover, multicentre trial. Participants: Sixty-four patients with ocular hypertension or open-angle glaucoma were randomised to two groups, after a 4-week washout period from their current topical drop regimen. Methods: Participants were randomised to tafluprost (Group 1; n = 33) or bimatoprost (Group 2; n = 31). At month 3, each group switched to the opposite treatment. IOP was evaluated at multiple timepoints. Main outcome measures: The primary outcome was difference in mean IOP between the two groups at the final visit. Secondary outcomes included change from baseline IOP at month 3 and month 6, difference in mean IOP at month 3 and difference in IOP at all timepoints. Safety outcomes included best-corrected visual acuity (BCVA), adverse events, ocular tolerability, optic nerve assessment and slit lamp biomicroscopy. Results: Both medications significantly lowered IOP at month 6 compared to baseline: 5.4 mmHg (27%) for tafluprost and 6.8 mmHg (33%) for bimatoprost (p < 0.0001). No significant differences in any of the safety measures (including conjunctival hypearemia) were detected. Conclusions and relevance: Bimatoprost produced a statistically significant greater IOP reduction compared to tafluprost with minimal to no difference in side effects. This should be borne in mind when weighing up the pros and cons of preserved versus preservative-free prostaglandin analogue therapy.
Testing the performance of risk prediction models to determine progression to referable diabetic retinopathy in an Irish type 2 diabetes cohort
(BMJ Publishing Group, 2021-04-26) Smith, John; Wright, David; Stratton, Irene; Scanlon, Peter; Lois, Noemi; Stratton, Irene; Scanlon, Peter; Additional Professional Scientific and Technical; Medical and Dental
Background /aims: To evaluate the performance of existing prediction models to determine risk of progression to referable diabetic retinopathy (RDR) using data from a prospective Irish cohort of people with type 2 diabetes (T2D). Methods: A cohort of 939 people with T2D followed prospectively was used to test the performance of risk prediction models developed in Gloucester, UK, and Iceland. Observed risk of progression to RDR in the Irish cohort was compared with that derived from each of the prediction models evaluated. Receiver operating characteristic curves assessed models' performance. Results: The cohort was followed for a total of 2929 person years during which 2906 screening episodes occurred. Among 939 individuals followed, there were 40 referrals (4%) for diabetic maculopathy, pre-proliferative DR and proliferative DR. The original Gloucester model, which includes results of two consecutive retinal screenings; a model incorporating, in addition, systemic biomarkers (HbA1c and serum cholesterol); and a model including results of one retinopathy screening, HbA1c, total cholesterol and duration of diabetes, had acceptable discriminatory power (area under the curve (AUC) of 0.69, 0.76 and 0.77, respectively). The Icelandic model, which combined retinopathy grading, duration and type of diabetes, HbA1c and systolic blood pressure, performed very similarly (AUC of 0.74). Conclusion: In an Irish cohort of people with T2D, the prediction models tested had an acceptable performance identifying those at risk of progression to RDR. These risk models would be useful in establishing more personalised screening intervals for people with T2D.
Remote supervision for simulated cataract surgery
(2021-04-11) Mamotra, Sunil; Jones, Rebecca; Rabiolo, Alessandro; Saleh, George; Ferris, John; Mamotra, Sunil; Jones, Rebecca; Rabiolo, Alessandro; Ferris, John; Medical and Dental
No abstract available
Aflibercept in clinical practice; visual acuity, injection numbers and adherence to treatment, for diabetic macular oedema in 21 UK hospitals over 3 years
(Springer Nature, 2021-07-09) Talks, James; stratton, irene; Peto, Tunde; Lotery, Andrew; Chakravarthy, Usha; Eleftheriadis, Haralabos; Izadi, Shahrnaz; Dhingra, Naren; Scanlon, Peter; Stratton, Irene; Scanlon, Peter; Additional Professional Scientific and Technical; Medical and Dental
Introduction Randomised controlled trials provide evidence that a treatment works. Real world evidence is required to assess if proven treatments are effective in practice. Method Retrospective data collection on patients given aflibercept for diabetic macular oedema over 3 years from 21 UK hospitals: visual acuity (VA); Index of multiple deprivation score (IMD); injection numbers; protocols used, compared as a cohort and between sites. Results Complete data: 1742 patients (from 2196 eligible) at 1 year, 860 (from 1270) at 2, 305 (from 506) at 3 years. The median VA improved from 65 to 71, 70, 70 (ETDRS letters) at 1, 2 and 3 years with 6, 9 and 12 injections, respectively. Loss to follow-up: 10% 1 year, 28.8% at 3. Centres varied: baseline: mean age 61–71 years (p < 0.0001); mean IMD score 15–37 (p < 0.0001); mean VA 49–68 (p < 0.0001). Only four centres provided a loading course of five injections at monthly intervals and one 6. This did not alter VA outcome at 1 year. Higher IMD was associated with younger age (p = 0.0023) and worse VA at baseline (p < 0.0001) not total number of injections or change in VA. Lower starting VA, higher IMD and older age were associated with lower adherence (p = 0.0010). Conclusions The data showed significant variation between treatment centres for starting age, VA and IMD which influenced adherence and chances of good VA. Once treatment was started IMD did not alter likelihood of improvement. Loading dose intensity did not alter outcome at one year.
Royal College of Ophthalmologists’ National Ophthalmology Database study of cataract surgery: report 8, cohort analysis of the relationship between intraoperative complications of cataract surgery and axial length
(BMJ Publishing Group, 2022-08-19) Day, Alexander; Norridge, Charlotte F. E.; Donachie, Paul Henry John; Barnes, Beth; Sparrow, John; Norridge, Charlotte; Donachie, Paul; Medical and Dental
Objectives To describe the relationships between axial length and intraoperative complications in patients undergoing cataract surgery. Design Cohort analysis of the Royal College of Ophthalmologists’ National Ophthalmology Database (RCOphth NOD). Setting 110 National Health Service Trusts in England, Health Boards in Wales, Independent Sector Treatment Centres and Guernsey. Participants 820 354 patients, aged 18 years or older, undergoing cataract surgery. Eligible operations were those from centres with at least 50 operations with a recorded axial length measurement and age at surgery between 1 April 2010 and 31 August 2019. Interventions Phacoemulsification where the primary intention was cataract surgery alone. Outcome measures Posterior capsule rupture (PCR) and other recorded intraoperative complications. Results 1 211 520 eligible operations were performed by 3210 surgeons. The baseline axial length was <21 mm (short eyes) for 17 170 (1.4%) eyes, 21–28 mm (medium eyes) for 1 182 513 (97.6%) eyes and >28 mm (long eyes) for 11 837 (1.0%) eyes. The median age at surgery was younger for patients with long eyes than those with short or medium eyes. The rate of any intraoperative complication was higher for short eyes than medium or long with complication rates of 4.5%, 2.9% and 3.3%, respectively (p<0.001). PCR occurred in 1.40% surgeries overall, and in 1.53%, 1.40% and 1.61% of short, medium and long eyes, respectively (p=0.043, not significant at the 1% level). Conclusions Overall PCR rates for cataract surgery in RCOphth NOD contributing centres are lower than previously reported and there is little change in PCR rates by axial length. Short eyes were more likely to have an intraoperative complication than medium or long eyes.
Ophthalmic surgery techniques can be simulated and supervised remotely in the home environment: a proof-of-concept report
(Springer Nature, 2021-06-28) Maubon, Laura; Mamtora, Sunil; Aggarwal, Kavita; Neo, Yan Ning; Khan, Saj; Lockington, David; Mamtora, Sunil; Medical and Dental
No abstract available
Prevalence and incidence of diabetic retinopathy (DR) in the UK population of Gloucestershire
(Wiley, 2021-06-28) Scanlon, Peter; Nevill, Clareece; Stratton, Irene; Maruti, Sonia; Masso-Gonzalez, Elvira; Sivaprasad, Sobha; Bailey, Clare; Ehrlich, Michael; Chong, Victor; Scanlon, Peter; Nevill, Clareece; Stratton, Irene; Medical and Dental; Additional Professional Scientific and Technical
Purpose To estimate prevalence and incidence of diabetic retinopathy (DR) in a UK region by severity between 2012 and 2016 and risk factors for progression to proliferative DR (PDR). Methods Electronic medical records from people with diabetes (PWD) ≥18 years seen at the Gloucestershire Diabetic Eye Screening Programme (GDESP) and the hospital eye clinic were analysed (HEC). Prevalence and incidence of DR per 100 PWD (%) by calendar year, grade and diabetes type were estimated using log-linear regression. Progression to PDR and associated risk factors were estimated using parametric survival analyses. Results Across the study period, 35 873 PWD had at least one DR assessment. They were aged 66 (56–75) years (median (interquartile range)), 57% male, 5 (1–10) years since diabetes diagnosis, 93% Type 2 diabetes. Prevalence of DR decreased from 38.9% (95% CI: 38.1%, 39.8%) in 2012 to 36.6% (95% CI: 35.9%, 37.3%) in 2016 (p < 0.001). Incidence of any DR decreased from 10.9% (95% CI: 10.4%, 11.5%) in 2013 to 8.5% (95% CI: 8.1%, 9.0%) in 2016 (p < 0.001). Prevalence of PDR decreased from 3.5% (95% CI: 3.3%, 3.8%) in 2012 to 3.1% (95% CI 2.9%, 3.3%) in 2016 (p = 0.008). Incidence of PDR did not change over time. HbA1c and bilateral moderate–severe NPDR were statistically significant risk factors associated with progression to PDR. Conclusions Incidence and prevalence of DR decreased between 2012 and 2016 in this well-characterized population of the UK.
Periocular Trichoblastoma: A Diagnostic Dilemma
(Karger Publishers, 2022-06-17) Gounder, Pav; Scantling-Birch, Yarrow; Caldwell, Carole; Bassey-Duke, Daisy; Craig, Paul; Madge, Simon; Craig, Paul; Medical and Dental
A 41-year-old woman presented with a large medial canthal lesion that extended over the midline. Excisional biopsy revealed a multinodular basaloid tumor, located within the dermis and subcutaneous fat that extended into skeletal muscle at the deep and peripheral margin. Histology was consistent with trichoblastoma. A review of the literature reveals a lack of specific and sensitive immunohistochemistry markers to establish the diagnosis of trichoblastoma. Following reconstruction, the patient has shown no signs of recurrence of the lesion at 24 months.
Intraoperative complications and visual outcomes of cataract surgery in patients with retinal vein occlusion: multicenter database study
(Lippincott, Williams & Wilkins, 2022-06-01) Ponder, Christian; Rather, Peyton; Soliman, Mohmed; Jabbehdari, Sayena; Neuhouser, Adam; Siddiqui, Mohammed; Yang, Yit; Sallam, Ahmed; Sallam, Ahmed; Medical and Dental
Purpose: To compare the visual outcomes and the rate of intraoperative complications in eyes with and without retinal vein occlusion (RVO) after phacoemulsification over a period of 15 years in a real-world clinical setting. Setting: 8 independent U.K. National Health Service ophthalmology departments. Design: Retrospective, multicenter cohort study. Methods: Eyes were classified based on the presence or absence of RVO. For analyzing visual acuity (VA) and the incidence of postoperative cystoid macular edema, eyes with any copathology, combined ocular surgical procedures, and intraoperative complications, or of diabetic patients were excluded. Results: Of 178 856 eyes, 1796 eyes with RVO preoperatively and 177 060 eyes without RVO were allocated to the RVO group and the reference group, respectively. Cataract surgery in eyes with RVO was associated with an improvement in the mean VA of 0.35 logMAR (3 to 4 Snellen lines), and a substantial gain (≥0.30 logMAR units [3 Snellen lines]) was achieved in 55.10% of eyes at 4 to 12 weeks postoperatively. The mean postoperative VA was worse in eyes with RVO compared with that in eyes without RVO at 4 to 12 weeks (logMAR 0.40 vs 0.12 [20/50 vs 20/25]; P < .0001). The proportion of eyes achieving a visual gain of ≥ 0.3 logMAR (3 Snellen lines) was also lower in eyes with RVO (55.10% vs 64.55%; P = .0076). There was no statistically significant difference in posterior capsule rupture rates between the 2 groups (1.73% vs 1.72%; P = .9741). Conclusions: Although postoperative vision improved significantly in eyes with RVO after cataract surgery, this improvement was worse than that achieved by eyes without RVO.
Why Is Continued Vision Loss Still a Problem in Some Patients With Diabetic Retinopathy, Despite Treatment?
(American Medical Association, 2022-04-01) Bressler, Susan; Scanlon, Peter; Pearce, Elizabeth; Scanlon, Peter; Medical and Dental
Evidence suggests that most patients with diabetic retinopathy (DR) who lose vision do so because of complications of proliferative diabetic retinopathy (PDR) or diabetic macular edema (DME). Diligent screening of patients for PDR and DME followed by administration of laser treatment, anti–vascular endothelial growth factor (VEGF) therapy, or surgery can greatly reduce the risk of vision loss from these conditions.1 However, some patients with DR continue to lose vision despite treatments that ameliorate DME or PDR. Even in the best of circumstances, such as those in the DRCR Retina Network Protocol T trial,2 4% of patients receiving aflibercept, 6% of patients receiving bevacizumab, and 2% of patients receiving ranibizumab had lost at least 10 letters (approximately 2 lines) of visual acuity at 2 years. In the same trial,2 among patients with a baseline visual acuity of 20/50 to 20/320, 9% of patients receiving aflibercept, 16% of patients receiving bevacizumab, and 15% of patients receiving ranibizumab had visual acuity of 20/80 or less at 2 years, while among patients with a baseline visual acuity of 20/32 to 20/40 at baseline, 6% of patients receiving aflibercept, 6% of patients receiving bevacizumab, and 3% of patients receiving ranibizumab had a visual acuity of 20/50 or less at 2 years.2 The precise incidence and reasons underlying progressive vision loss in eyes that have been treated for either PDR or DME remain unclear and may be confounded by non–DR-related pathology such as cataracts, glaucoma, or age-related macular degeneration.
Impact of Different Literature-based Hypotony Failure Criteria on Success Rates of Glaucoma Surgery
(Association for Research in Vision and Ophthalmology, 2023-06) Rabiolo, Alessandro; Triolo, Giacinto; Ghirardi, Alessandro; Anand, Nitin; Montesano, Giovanni; Virgili, Gianni; Stefano, De Cillà; Anand, Nitin; Medical and Dental
Purpose : To evaluate the impact of varying hypotony failure criteria on surgical success rates in a large cohort of patients undergoing glaucoma surgery. Methods : We identified fifty different hypotony criteria through a systematic literature review (Prospero protocol ID: CRD42017079778). We then applied the various hypotony definitions to a cohort of 1,765 eyes (1,385 patients) undergoing deep sclerectomy (DS) with or without cataract extraction between 2001 and 2020 in 2 UK centers and used them as failure criteria. Additional failure criteria were: IOP>21 mmHg or <20% IOP reduction from baseline in two consecutive postoperative visits >3 months after surgery, reoperation for glaucoma, and loss of light perception. We calculated Kaplan-Meier surgical success rates, and we tested differences in success rates as a function of the hypotony criteria with clustered Cox models. We conducted all analyses for each criterion and hypotony type (i.e., numerical [intraocular pressure threshold], clinical [clinical manifestations of hypotony], mixed [ combination of numerical and/or clinical criteria]). Results : Success rates greatly varied as a function of hypotony criteria used, ranging between 15.8-70.8%, 12.3-62.4%, and 11.3-57.5% at 3, 5, and 7 years, respectively (Fig 1). In comparison to no hypotony failure criteria (Fig 2A), numerical hypotony had the greatest impact on the calculated risk of failure (HR [95% confidence interval (CI): 1.75 [1.48-1.60], p<0.001), followed by mixed hypotony (HR [95%CI): 1.56 [1.43-1.69], p<0.001) and clinical hypotony (HR [95%CI): 1.15 [1.05-1.27], p=0.003). Differences among clinical, mixed, and numerical hypotony failure rates were significant between all pairs (p=0.02 or below). Every hypotony criterion had higher failure risk than no hypotony criterion, but the magnitude of the effect varied as a function of the specific criterion used, with hazard ratios (HRs) ranging between 1.02 and 13.30 (compared to not using any hypotony criterion). Conclusions : Glaucoma surgery success is greatly influenced by the hypotony criteria chosen. Numerical hypotony leads to higher failure rates than clinical hypotony. Its use as a failure criterion may underestimate glaucoma surgery success rates, especially those techniques more likely to reach low IOP values. Standardizing glaucoma surgery failure criteria with a focus on clinically relevant hypotony manifestations is needed.
Global versus localized association of reticular pseudodrusen with relative ellipsoid zone reflectivity in intermediate age-related macular degeneration
(Association for Research in Vision and Ophthalmology, 2023-06-01) Thiele, Sarah; Behning, Charlotte; Liermann, Yannick; Sassmannshausen, Marlene; Weinhold, Leonie; Isselmann, Ben; Schmid, Matthias; Finger, Robert; Schmitz-Valckenberg, Steffen; Pfau, Maximilian; Luu, Chi; Holz, Frank; Thiele, Sarah; Medical and Dental
Purpose : The relative ellipsoid zone reflectivity (rEZR) is an indicator for outer retinal integrity on spectral-domain optical coherence tomography (SD-OCT). In global (eye level) analyses, reticular pseudodrusen (RPD) are cross-sectionally associated with a more reduced rEZR in intermediate age-related macular degeneration (iAMD) eyes. Further, rEZR decreases over time more rapidly in eyes with vs. without RPD. This study aimed to assess the spatial impact of RPD on the rEZR. Methods : The rEZR [arbitrary units, AU] was determined in raw SD-OCT volume scans (241 B-scans, field size 30°x25°) from baseline visit of the MACUSTAR study. RPDs’ presence topographical information was obtained by its area’s manual annotation in infrared imaging. Other iAMD features, including pigmentary abnormalities (PA) and the RPEDC volume were also determined. Linear mixed-effects models with the rEZR as the dependent variable were applied to evaluate the impact of global vs. spatial vs. global+spatial RPD presence on the localized rEZR (with covariates adjusting for age and eccentricity). Results : A total of 164 eyes of 164 patients (mean±SD age: 71.3±7.52 years) of the iAMD MACUSTAR study cohort were included. The global presence of RPD was associated with a reduced rEZR of -6.45 AU (95%-CI: -12.24;-0.67 [p=0.029]). The presence of PA was also associated with an rEZR reduction (-3.91 AU [-8.52;0.71 (p=0.097)] as well as an RPEDC volume [mm3] increase (-2.49 AU [-39.23;34.24 (p=0.894)]. Considered topographically, RPD exhibited an association with the rEZR of -11.74 AU (-11.90;-11.58 [p<0.001]), the RPEDC volume of -1.87 AU (-38.15;34.40 [p=0.919]) and the presence of PA of -4.26 AU (-8.79;0.28 [p=0.066]). Taken further the global and topographical RPD presence simultaneously into account, only RPD were shown to exhibit an association with the rEZR when considered topographically as demonstrated by an rEZR decrease of -11.74 AU (-11.90;-11.58 [p<0.001]). Conclusions : The rEZR exhibited a significant association with the presence of RPD, a high-risk structural phenotype for AMD progression. This was even more pronounced when the topographical information of RPD within an eye was also taken into account. Ongoing studies assess the prognostic value of the rEZR for progression to late-stage AMD manifestations.
Assessing Hypotony Definitions used as Failure Criteria in Glaucoma Surgical Studies
(Association for Research in Vision and Ophthalmology, 2023-06-01) Triolo, Giacinto; Ghirardi, Alessandro; Montesano, Giovanni; Anand, Nitin; Virgili, Gianni; De Cilla, Stefano; Rabiolo, Alessandro; Anand, Nitin; Medical and Dental
Purpose : To systematically review hypotony failure criteria used in the glaucoma surgical studies. Methods : We performed a systematic review on MEDLINE searching for glaucoma surgical techniques providing ab externo (e.g., trabeculectomy, glaucoma drainage devices, deep sclerectomy, Preserflo MicroShunt, Express shunt) or ab interno (e.g., Xen Gel) subconjunctival filtration. Patients receiving glaucoma surgeries targeting trabecular meshwork and suprachoroidal space were not included. Both stand-alone and combined surgeries were included. Only studies reporting success rates were included. Only studies published in English and conducted on human subjects were included. We filtered search results for articles published between January 1, 2010, to November 21, 2022, and selected the following article types: clinical study, clinical trial (all types), comparative study, multicenter study, and observational study. Two independent investigators screened titles and abstracts to select studies to include and extracted hypotony definitions (if any) used as surgical failure criteria. Discordance was solved by open adjudication, and in case of disagreement, a third investigator was involved in making a final decision. Study outcomes were specific hypotony definitions, their type (i.e., numerical, clinical, mixed), and their prevalence in the current literature. Results : Among the 2,503 studies identified through database search, 278 were eligible (Fig 1). Ninety-nine (35.6%) studies had no hypotony failure criteria; numerical hypotony (IOP below a certain threshold (expressed in mmHg), regardless of hypotony complications) was the most used failure criterion (157 studies [56.5%]). A minority of studies had clinical complications of hypotony among failure criteria, isolated (3 studies [1.1%]) or in combination with a low IOP cutoff (19 studies [6.8%]). Fifty different specific hypotony failure criteria were found (Fig 2), with IOP<6 mmHg, IOP<6 mmHg on ≥2 consecutive visits after 3 months, and IOP<5 mmHg being the most used failure criteria in 41 (14.7%), 38 (13.7%), and 13 (4.7%) studies, respectively. Conclusions : Hypotony failure criteria are highly heterogenous in current glaucoma literature, with few studies focusing on clinically relevant signs of hypotony. Further studies are warranted to examine the impact of different hypotony definitions on surgical success rates.
Delivering topical IL-33 with a cell penetrating peptide to treat neovascular age-related macular degeneration.
(Association for Research in Vision and Ophthalmology) Thomas, Chloe; Theodoropoulou, Sofia; Weston, Christopher; Cooklin, Jessica; Copland, Dave; Dick, Andrew; Denniston, Alastair; Hill, Lisa; Theodoropoulou, Sofia; Medical and Dental
Abstract Purpose : Age-related macular degeneration (AMD) is the most common cause of central vision loss globally. Neovascular AMD (nAMD) is currently treated with regular intraocular injections of anti-VEGF therapies, to which some patients are unresponsive, while multiple injections are not well-tolerated and can cause complications including infection. We previously demonstrated intraocular delivery of recombinant interleukin-33 (IL-33) reduced laser-induced choroidal neovascularisation (CNV) pathology in a mouse model, offering a promising new treatment. Additionally, an eyedrop of bevacizumab complexed to a cell penetrating peptide (CPP) reduced lesion size equivalent to intravitreal injection delivery in a mouse CNV model. Thus, we propose combining IL-33 immunotherapy and our delivery agent, IL-33+CPP6, to be developed as a topical formulation. Methods : Human recombinant IL-33 was complexed with the CPP to assess cell toxicity, MTT and LDH assays for 48h over a dose range of 0.2–200pg/ul in cultured human RPE (ARPE-19) and human ocular choroidal fibroblasts (HOCFs). HOCF scratch assay was performed and cells treated with media, vehicle, CPP, IL-33 (200pg/ul) or IL-33+CPP and imaged over 48h. The percentage wound closure (end vs start width) was measured using Cell IQ software. N=3, repeated on 3 independent occasions. Results : IL-33+CPP complexes were non-toxic to ARPE-19 or HOCFs across a dose range (0.2–200pg/ul). In ARPE-19 cells and HOCFs, there were no differences after treatment in total viable cell number (total cell LDH; P=0.8306, P=0.9641, ANOVA) or significant changes in cellular viability (MTT assay; P=0.9772, P=0.2910, ANOVA). Importantly IL-33+CPP had equivalent significant biological effects to IL-33 alone, reducing wound healing (~15% less wound closure at 48h vs media/vehicle/CPP6). Across groups in scratch assay, there was a significant effect on percentage wound closure (P=0.0430, ANOVA), with borderline significance in post-hoc analysis (Tukey) between media and IL-33 (P=0.0529) and IL-33+CPP (P=0.0639) treatments. Conclusions : IL-33+CPP is a promising treatment in a formulation of a drop for nAMD. IL-33+CPP demonstrates non-toxicity and has preserved biological effect as direct IL-33 administration. Further experiments will assess ocular penetration and in vivo efficacy of our topical administration.
Laser goniopuncture after deep sclerectomy: incidence, long-term outcomes and risk factors for failure
(BMJ Publishing Group, 2021-07-20) Rabiolo, Alessandro; Leadbetter, Duncan; Kirk, Jonathan; Anand, Nitin; Rabiolo, Alessandro; Leadbetter, Duncan; Kirk, Jonathan; Anand, Nitin; Medical and Dental
Aims: To report the incidence, risk factors and long-term outcomes of laser goniopuncture (LGP) in patients with previous deep sclerectomy (DS). Methods: Retrospective cohort study of 1765 eyes (1385 patients) undergoing DS with or without cataract surgery between 2001 and 2020 in two UK institutions. Kaplan-Meier was used to estimate LGP incidence. DS success after LGP was calculated for criteria A, B, and C defined as intraocular pressure (IOP) of ≤18, ≤15 and ≤12 mm Hg with 20%, 25% and 30% reduction, respectively. Cox regression was used to investigate factors associated with the risk of failure. Results: LGP had an estimated incidence of 33.3% (30.9%-35.6%), 56.3% (53.5%-58.9%) and 62.8% (59.7%-65.6%) at 1, 3, 5 years, respectively. Mean (±SD) IOP significantly (p<0.001) decreased from 21.2 (±6.0) mm Hg pre-LGP to 13.8 (±5.2) mm Hg and 12.9 (±4.7) mm Hg at 3 and 5 years post-LGP, respectively. Success rates at 3 and 5 years were, respectively, 40.9% (37.5%-44.6%) and 33.7% (30.3%-37.6%) for criterion A; 27.1% (24.0%-30.5%) and 22.3% (19.3%-25.7%) for criterion B and 13.9% (11.6%-16.7%) and 11.6% (9.5%-14.3%) for criterion C. In all models, higher pre-LGP IOP (p<0.001) and higher pre-LGP medication number (p<0.001) were associated with increased failure, while male gender (p≤0.004), intraoperative mitomycin C (p≤0.031), longer interval between DS and LGP (p≤0.01) with reduced failure. Conclusion: Most patients undergoing DS will eventually require LGP. LGP is effective at rescuing eyes with a failing DS. This study identifies several factors associated with LGP outcomes, knowledge of which may help clinicians predict LGP success.
Individualised variable-interval risk-based screening in diabetic retinopathy: the ISDR research programme including RCT
(NIHR Journals Library, 2023-10-01) Harding, Simon; Alshukri, Ayesh; Appelbe, Duncan; Broadbent, Deborah; Burgess, Philip; Byrne, Paula; Cheyne, Christopher; Eleuteri, Antonio; Fisher, Anthony; Garcia-Finana, Marta; Gabbay, Mark; James, Marilyn; Lathe, James; Moitt, Tracy; Mehrdad Mobayen, Rahni; Roberts, John; Sampson, Christopher; Seddon, Daniel; Stratton, Irene; Thetford, Clare; Vazquez-Arango, Pilar; Vora, Jiten; Wang, Amu; Williamson, Paula; Stratton, Irene; Additional Professional Scientific and Technical
Background: Systematic annual screening for sight-threatening diabetic retinopathy is established in several countries but is resource intensive. Personalised (individualised) medicine offers the opportunity to extend screening intervals for people at low risk of progression and to target high-risk groups. However, significant concern exists among all stakeholders around the safety of changing programmes. Evidence to guide decisions is limited, with, to the best of our knowledge, no randomised controlled trials to date. Objectives: To develop an individualised approach to screening for sight-threatening diabetic retinopathy and test its acceptability, safety, efficacy and cost-effectiveness. To estimate the changing incidence of patient-centred outcomes. Design: A risk calculation engine; a randomised controlled trial, including a within-trial cost-effectiveness study; a qualitative acceptability study; and an observational epidemiological cohort study were developed. A patient and public group was involved in design and interpretation. Setting: A screening programme in an English health district of around 450,000 people. Participants: People with diabetes aged ≥ 12 years registered with primary care practices in Liverpool. Interventions: The risk calculation engine estimated each participant’s risk at each visit of progression to screen-positive diabetic retinopathy (individualised intervention group) and allocated their next appointment at 6, 12 or 24 months (high, medium or low risk, respectively). Main outcome measures: The randomised controlled trial primary outcome was attendance at first follow-up assessing the safety of individualised compared with usual screening. Secondary outcomes were overall attendance, rates of screen-positive and sight-threatening diabetic retinopathy, and measures of visual impairment. Cost-effectiveness outcomes were cost/quality-adjusted life year and incremental cost savings. Cohort study outcomes were rates of screen-positive diabetic retinopathy and sight-threatening diabetic retinopathy. Data sources: Local screening programme (retinopathy), primary care (demographic, clinical) and hospital outcomes. Methods: A seven-person patient and public involvement group was recruited. Data were linked into a purpose-built dynamic data warehouse. In the risk assessment, the risk calculation engine used patient-embedded covariate data, a continuous Markov model, 5-year historical local population data, and most recent individual demographic, retina and clinical data to predict risk of future progression to screen-positive. The randomised controlled trial was a masked, two-arm, parallel assignment, equivalence randomised controlled trial, with an independent trials unit and 1 : 1 allocation to individualised screening (6, 12 or 24 months, determined by risk calculation engine at each visit) or annual screening (control). Cost-effectiveness was assessed using a within-trial analysis over a 2-year time horizon, including NHS and societal perspectives and costs directly observed within the randomised controlled trial. Acceptability was assessed by purposive sampling of 60 people with diabetes and 21 healthcare professionals with semistructured interviews analysed thematically; this was a constant comparative method until saturation. The cohort was an 11-year retrospective/prospective screening population data set. Results: In the randomised controlled trial, 4534 participants were randomised: 2097 out of 2265 in the individualised arm (92.6%) and 2224 out of 2269 in the control arm (98.0%) remained after withdrawals. Attendance rates at first follow-up were equivalent (individualised 83.6%, control 84.7%) (difference –1.0%, 95% confidence interval –3.2% to 1.2%). Sight-threatening diabetic retinopathy detection rates were non-inferior: individualised 1.4%, control 1.7% (difference –0.3%, 95% confidence interval –1.1% to 0.5%). In the cost-effectiveness analysis, the mean differences in complete-case quality-adjusted life years (EuroQol-5 Dimensions, five-level version, and Health Utilities Index Mark 3) did not significantly differ from zero. Incremental cost savings per person not including treatment costs were from the NHS perspective £17.34 (confidence interval £17.02 to £17.67) and the societal perspective £23.11 (confidence interval £22.73 to £23.53). In the individualised arm, 43.2% fewer screening appointments were required. In terms of acceptability, changing to variable intervals was acceptable for the majority of people with diabetes and health-care professionals. Annual screening was perceived as unsustainable and an inefficient use of resources. Many people with diabetes and healthcare professionals expressed concerns that 2-year screening intervals may detect referable eye disease too late and might have a negative effect on perceptions about the importance of attendance and diabetes care. The 6-month interval was perceived positively. Among people with dementia, there was considerable misunderstanding about eye-related appointments and care. In the cohort study, the numbers of participants (total 28,384) rose over the 11 years (2006/7, n = 6637; 2016/17, n = 14,864). Annual incidences ranged as follows: screen-positive 4.4–10.6%, due to diabetic retinopathy 2.3–4.6% and sight-threatening diabetic retinopathy 1.3–2.2%. The proportions of screen-positive fell steadily but sight-threatening diabetic retinopathy rates remained stable. Limitations: Our findings apply to a single city-wide established English screening programme of mostly white people with diabetes. The cost-effectiveness analysis was over a short timeline for a long-standing disease; the study, however, was designed to test the safety and effectiveness of the screening regimen, not the cost-effectiveness of screening compared with no screening. Cohort data collection was partly retrospective: data were unavailable on people who had developed sight-threatening diabetic retinopathy or died prior to 2013. Conclusions: Our randomised controlled trial can reassure stakeholders involved in diabetes care that extended intervals and personalised screening is feasible, where data linkage is possible, and can be safely introduced in established screening programmes with potential cost savings compared with annual screening. Rates of screen-positive diabetic retinopathy and sight-threatening diabetic retinopathy are low and show consistent falls over time. Involvement of patients in research is crucial to success. Future work: Future work could include external validation with other programmes followed by scale-up of individualised screening outside a research setting and economic modelling beyond the 2-year time horizon. Trial registration: This trial is registered as ISRCTN87561257. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 11, No. 6. See the NIHR Journals Library website for further project information.

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