Real-world service costs for neovascular-AMD clinics in the United Kingdom: structured literature review and scenario analysis.

OBJECTIVE: Current cost-effectiveness analyses (CEA) emphasize drug costs as the differentiator between NICE recommended anti-VEGF treatments but may neglect real-world non-drug costs of running nAMD services in the UK. To address this, this study identified real-world non-drug service cost items relevant to UK NHS nAMD clinics, including costs arising from operational strain (demand exceeding capacity). METHODS: Cost items were identified by a structured literature review of peer-reviewed and grey literature, and an expert panel of 10 UK-based ophthalmologists with relevance to real-world practice. These items underwent meta-synthesis and were then determined in a consensus exercise. RESULTS: Of 237 cost items identified, 217 (91.6%) met the consensus threshold of >0.51 and were included in the nAMD Service Non-Drug Cost Instrument (nAS). Sensitivity of cost items taken from UK Health Technology Assessment (HTA) using the nAS as the reference standard was low (HTAmin: 1.84%, 95% CI 0.50-4.65%; HTAmax: 70.51%, 95% CI 63.96-76.49%). False negative rates showed variable likelihood of misclassifying a service by cost burden depending on prevalence. Scenario analysis using cost magnitudes estimated annual per-patient clinic cost at £845 (within capacity) to £13,960 (under strain) compared to an HTAmin estimate of £210. Accounting for cost of strain under an assumed 50% increase in health resource utilization influenced cost-effectiveness in a hypothetical genericisation scenario. CONCLUSION: Findings suggested that HTA underestimates UK NHS nAMD clinic cost burden with cost of strain contributing substantial additional unmeasured expense with impact on CEA. Given potential undertreatment due to strain, durability is suggested as one of the relevant factors in CEA of nAMD anti-VEGF treatments due to robustness under limited capacity conditions affecting UK ophthalmology services.

When considering how well treatments work versus how much they cost, the focus is usually only on the price of the medicine itself. However, other real-world costs exist. In the UK, when treating certain eye problems such as neovascular age-related macular degeneration (nAMD), there are additional expenses related to running clinics and managing treatments that often go unnoticed. To get a better understanding of these hidden costs, the study examined factors like clinic workload and the extra expenses that come with it. Ten eye doctors in the UK were consulted for their expert opinions and numerous research papers were reviewed to identify these additional costs. The study grouped different costs in a tool called the nAMD Service Non-Drug Cost Instrument (nAS). When the findings of the nAS tool were compared to the usual methods of calculating costs, it was found that the conventional approach overlooked many of the actual expenses. Busy clinics face unique challenges, such as higher operational costs associated with staffing for extended hours, emergency appointments, extended waiting times and the potential to miss optimal treatment windows. This can lead to disease progression and the onset of comorbidities, which require more complex and costly treatments. Recognizing these real costs is crucial when making decisions about treatments, especially when treatments require more frequent visits to eye clinics. This study emphasizes the importance of considering all expenses, not just the obvious ones like medication and doctor visits when determining the most effective way to manage eye conditions like nAMD in the UK.

Practical implementation of a q4-q16 aflibercept treat-and-extend pathway for the treatment of neovascular age-related macular degeneration: Updated guidance from a UK expert panel.

OBJECTIVES: This report, based on guidance from a panel of UK retina specialists, introduces a revised intravitreal aflibercept (IVT-AFL) treat-and-extend (T&E) pathway for the treatment of neovascular age-related macular degeneration (nAMD). The T&E pathway incorporates the updated IVT-AFL label (April 2021) allowing flexible treatment intervals of 4 weeks to 16 weeks, after three initiation doses and a further dose after 8 weeks. Practical guidance is provided on the clinical implementation of the revised pathway, with the aim of supporting clinical decision-making to benefit patients and addressing capacity issues in nAMD services. METHODS: Three structured round-table meetings of UK retina specialists were held online on 19 May, 16 June and 13 October 2021. These meetings were organised and funded by Bayer. RESULTS: The authors revised the previously published consensus pathway to reflect the changes to the IVT-AFL label and developed guidelines for the implementation of the pathway in UK clinical practice. The guidelines include topics such as recommendations for extending patients with 2- or 4-week adjustments, extending patients to 16-week treatment intervals, managing fellow eye involvement, and reducing treatment intervals for patients with particularly active disease. CONCLUSIONS: The revised IVT-AFL T&E nAMD pathway offers guidance to clinicians seeking to increase the dosing flexibility of IVT-AFL, with 4- to 16-week treatment intervals, in line with the updated IVT-AFL label, to meet the continually evolving demands of nAMD service provision.

Identifying early symptoms of choroidal neovascularisation in second eyes of patients with unilateral wet age related macular degeneration using a telephone evaluation method.

BACKGROUND/OBJECTIVES: Patients undergoing intravitreal injections for nAMD are often anxious about early detection of nAMD in their fellow eyes. The purpose of this study was to evaluate a home-based telephone method for helping patients to monitor for symptoms of second eye involvement. SUBJECTS/METHODS: Using a five-staged evaluation tool, telephone-assisted evaluations were repeatedly performed on the patients' fellow eyes every 4 weeks for 1 year. A decision on presence or absence of nAMD was made after each telephone evaluation. Slitlamp examination and OCT scan were performed at 3, 6, 9 and 12 months or whenever nAMD was suspected from the telephone evaluation. The sensitivity and specificity values were calculated from the true and false positive and negative rates of each of the five composite stages. RESULTS: In total, 514 telephone episodes comprising 2570 evaluations were conducted on fellow eyes of 50 patients over one year. Three patients (6%) developed nAMD in fellow eyes. The sensitivity of all of the stages was low (33.3%). The specificity of the five stages ranged from 91.3% to 98.6%. The highest specificity was achieved by the near acuity component of the tool. CONCLUSIONS: We were unable to demonstrate a high sensitivity for the five-staged tool but the near acuity component of this tool had a very high specificity. This could have potential for "ruling out" nAMD and reducing the burden of false positive episodes for a large group of patients who are at risk of developing nAMD in their second eyes.

Ocular surface effects of repeated application of povidone iodine in patients receiving frequent intravitreal injections.

BACKGROUND: The aim of this study was to investigate the patient reported symptoms and objective signs of tear film and ocular surface abnormalities experienced by patients undergoing repeated exposure to povidone iodine as a consequence of requiring frequent intravitreal injections for wet macular degeneration. METHODS: This was a prospective study of consecutive patients who had received recent povidone 5% solution for sterile preparation of intravitreal injection less than 3 months prior to inclusion with a total of at least 3 intravitreal injections for macular degeneration. Each patient had one study eye which was undergoing regular intravitreal injection and a fellow eye which was not undergoing any injections. Each patient underwent evaluations of various tear film parameters on a single occasion for both eyes. The primary outcome was severity of dry eye symptoms as measured by the Schein dry eye questionnaire. The secondary outcomes were tear film osmolarity and corneal punctate staining using the Oxford Grading Scale. RESULTS: A total of 90 patients were included in the study. 43.3% n = 39, were using ocular lubricating medication on a regular basis. A significantly greater proportion of study eyes had a Schein dry eye questionnaire score of 7 or higher; 12.2%, n = 11 amongst study eyes vs 4.4%, n = 4 amongst control, fellow eyes (p < 0.05). In terms of secondary outcomes, the study eyes had a slightly higher mean tear film osmolality compared to control, fellow eyes: 305.5 ± 1.7 in study eyes vs 302 ± 1.6 in control eyes although this difference was not statistically significant (p = 0.087). The study eyes had statistically significantly worse corneal staining as determined by the Oxford grading scale; 0.69 in study eyes vs 0.58 in control, fellow eyes (p = 0.02). CONCLUSION: Our results confirm the detrimental impact of repeated application of povidone iodine for intravitreal injection procedures on symptoms of dry eyes as experienced and reported by patients.

Retinal embolic events: frequency and impact following transcatheter aortic valve implantation (TAVI) for aortic stenosis.

OBJECTIVES: Transcatheter aortic valve implantation (TAVI) is an established treatment for patients with severe symptomatic aortic stenosis. It has a cerebrovascular accident rate of about 5% but the effect on retinal embolic events has not been previously reported. This study investigated the occurrence of retinal emboli following TAVI. METHODS AND ANALYSIS: In this prospective observational study, 20 patients underwent full ophthalmic examination to assess retinal embolic events prior to TAVI and at 48 hours and 1 month post-TAVI. RESULTS: At 48 hours post-TAVI, one patient had a new cotton wool spot in the right eye. At 1 month, another two patients had new retinal emboli events in at least one eye and a fourth patient developed retinal splinter haemorrhages in the right eye. CONCLUSION: Retinal embolic events and new retinal abnormalities following TAVI occurred in 15% and 20% of our cohort, respectively, without any associated retinal damage or significant visual problems. Retinal evaluation may be a useful surrogate test for cerebral embolisation in future studies assessing the utility of new valve prostheses and embolic protection devices.

Clinical characteristics and selection of treatment modality for patients with vitreomacular traction: real-world implementation of NICE guidance (TA297).

AIM: To investigate the qualitative aspects in patient selection and the quantitative impact of disease burden in real world treatment of vitreomacular traction (VMT) and implementation of the National Institute for Health and Care Excellence (NICE) guidance (TA297). METHODS: A monocentric, retrospective review of consecutive patients undergoing optical coherence tomography (OCT) imaging over a 3 month period. Patients with VMT in at least one eye were identified for further data collection on laterality, visual acuity, symptoms, presence of epiretinal membrane, macular hole and treatment selection. RESULTS: A total of 3472 patients underwent OCT imaging with a total of 6878 eyes scanned. Out of 87 patients, 74 patients had unilateral VMT (38 right, 36 left) and 13 patients had bilateral VMT. Eighteen patients with unilateral VMT satisfied NICE criteria of severe sight problems in the affected eye. Eight were managed for a coexisting pathology, one refused treatment, one patient did not attend, two closed spontaneously, and one received ocriplasmin prior to the study start date. Only two patients with unilateral VMT received ocriplasmin and three underwent vitrectomy. Those failing to meet NICE criteria for unilateral VMT were predominantly asymptomatic (n=49) or had coexisting ERM (n=5) or both (n=2). CONCLUSION: Ocriplasmin provides an alternative treatment for patients with symptomatic VMT. Our data shows that the majority of patients with VMT do not meet NICE TA297 primarily due to lack of symptoms. Those meeting NICE criteria, but not treated, tended to have coexisting macular pathology. Variation in patient selection due to subjective factors not outlined in NICE guidance suggests that real world outcomes of ocriplasmin therapy should be interpreted with caution.

Safety of intravitreal ocriplasmin for focal vitreomacular adhesion in patients with exudative age-related macular degeneration.

PURPOSE: The evaluation of the safety and preliminary efficacy of 125 µg ocriplasmin intravitreal injection in patients with focal vitreomacular adhesion (VMA) and exudative age-related macular degeneration (AMD). DESIGN: Randomized, sham-injection controlled, double-masked, multicenter, phase II trial. PARTICIPANTS: A total of 100 patients with VMA and wet AMD were randomized 3:1 to receive 125 µg ocriplasmin intravitreal injection or sham injection. METHODS: Study treatment was administered in the mid-vitreous cavity by injection. Post-treatment safety and efficacy assessments were made at baseline and on days 7, 14, and 28 and months 3, 6, and 12 after injection. Secondary efficacy end points were exploratory in nature. MAIN OUTCOME MEASURES: The safety and tolerability of ocriplasmin were evaluated. The primary efficacy end point was the proportion of patients with VMA release at day 28 after injection. Secondary end points reported included VMA release over time, total posterior vitreous detachment (PVD), change in visual acuity from baseline, and number of anti-vascular endothelial growth factor (VEGF) injections. RESULTS: The safety of ocriplasmin in patients with VMA and wet AMD was shown to be comparable to the known safety profile, with the majority of adverse events in the study eye occurring in the first 7 days after study treatment. A greater proportion of patients achieved VMA resolution and total PVD at month 12 with ocriplasmin compared with sham treatment. There was a decrease in the number of anti-VEGF injections with ocriplasmin at month 12 compared with the sham group, although no differences in visual acuity were observed. CONCLUSIONS: Ocriplasmin treatment in this population seems to be generally safe and well tolerated and resulted in more patients achieving VMA resolution and PVD with less anti-VEGF use compared with sham treatment.

Bilateral visual outcomes and service utilization of patients treated for 3 years with ranibizumab for neovascular age-related macular degeneration.

BACKGROUND: The aim of this study was to describe bilateral visual outcomes and the effect of incomplete follow-up after 3 years of ranibizumab therapy for neovascular age-related macular degeneration. Secondarily, the demands on service provision over a 3-year period were described. METHODS: Data on visual acuity, hospital visits, and injections were collected over 36 months on consecutive patients commencing treatment over a 9-month period. Visual outcome was determined for 1) all patients, using last observation carried forward for missed visits due to early discontinuation and 2) only those patients completing full 36-month follow-up. RESULTS: Over 3 years, 120 patients cumulatively attended hospital for 1,823 noninjection visits and 1,365 injection visits. A visual acuity loss of <15 letters (L) was experienced by 78.2% of patients. For all patients (n=120), there was a mean loss of 1.68 L using last observation carried forward for missing values. Excluding five patients who died and 30 who discontinued follow-up, mean gain was 1.47 L. In bilateral cases, final acuity was on average 9 L better in second eyes compared to first eyes. Also, 91% of better-seeing eyes continued to be the better-seeing eye. CONCLUSION: We have demonstrated our approach to describing the long-term service provision and visual outcomes of ranibizumab therapy for neovascular age-related macular degeneration in a consecutive cohort of patients. Although there was a heavy burden with very frequent injections and clinic visits, patients can expect a good level of visual stability and a very high chance of maintaining their better-seeing eye for up to 3 years.

Differences in the topographic profiles of retinal thickening in eyes with and without serous macular detachment associated with diabetic macular oedema.

PURPOSE: To investigate if cases of diabetic macular oedema (DMO) associated with serous macular detachment (SMD) have a different topographic profile of retinal thickening compared with DMO cases not associated with SMD. METHODS: Optical coherence tomography scans of 152 eyes from 152 patients with centre-involving DMO and central subfield thickness >350 µm were identified. Measurements were taken of the neural retina at the highest point of thickening within the central subfield (H) and lateral extent of retina thicker than 350 µm (W). Group means were compared between eyes with SMD and eyes without SMD. RESULTS: SMD was present in 55 eyes (36%). H was lower in eyes with SMD than in eyes without SMD (396 µm vs 550 µm, p<0.001) while W was higher in eyes with SMD compared with eyes without SMD (4.74 mm vs 4.18 mm, p=0.011). CONCLUSIONS: There were distinct differences in topographical profiles of retinal thickening between eyes with SMD and eyes without SMD. These findings suggest a possible mechanical basis for the pathogenesis of SMD in DMO.

A Case of Candida albicans Endophthalmitis with No Predisposing Risk Factors and a Distant Source of Infection.

PURPOSE: To report a case of Candida albicans endophthalmitis with no identifiable predisposing risk factors. CASE REPORT: A 57-year-old male presented with a 3-day history of worsening floaters and reduced visual acuity. Fundoscopy and optical coherence tomography showed presence of fluffy white preretinal and intraretinal infiltrates. With no past medical history or evidence of immunosuppression but having travelled abroad and suffered from diarrhoea, fungal aetiology was thought to be unlikely and as a result, treatment was commenced for toxoplasma. Despite treatment, his vision did not improve. Initial investigations including inflammatory markers, serology for toxoplasmosis, blood culture, chest radiograph and aqueous sampling could not identify a source of infection. However, polymerase chain reaction results from vitreous sampling revealed C. albicans. As a result, the patient was treated with intravenous voriconazole and intravitreal amphotericin B. As initial clinical improvement was limited, a vitrectomy was performed with further intravitreal amphotericin B. Clinical improvement was rapid following vitrectomy. After repeated Gram staining and culture of infected toenails, Gram-positive yeast cells were isolated. CONCLUSION: Although C. albicans is a frequent cause of endogenous endophthalmitis, patients often have one or more predisposing systemic condition assisting the diagnosis. The present case illustrates that (1) even in the absence of any predisposing risk factors, C. albicans should be considered as a possible differential diagnosis in recalcitrant uveitis, and (2) endogenous candida endophthalmitis can be a result of fungal infections from distant sites such as the toenails.

A Rare Presentation of Occult Sinusitis: Upper Eyelid Fistula.

Sinus disease can present in a variety of ways and may occur in individuals who are not otherwise aware that they have problems (occult sinusitis). An unusual presentation of occult frontal sinus disease in a 64-year-old patient was reported. A fistulous communication with the upper lid, causing a persistent abscess. There was a 6-month delay in making the correct diagnosis and the patient was treated with repeated courses of antibiotics and even an incision and drainage procedure. Finally, the correct diagnosis was made following CT imaging and the patient underwent functional endoscopic sinus surgery which closed the communication, but left the patient with a tight upper lid, which required further oculoplastic surgery. The patient was pleased with the final visual outcome and the fistula remained closed.