Impact of treat and extend criteria on proportions that can be extended after loading phase of 2 mg aflibercept therapy for neovascular age related macular degeneration: PRECISE Report 5.

OBJECTIVE: To study the impact of definitions of various treatment extension criteria on the proportion of patients who could be extended at their first visit after the loading phase of 2 mg aflibercept therapy for neovascular age related macular degeneration (nAMD). METHODS: Patients with nAMD initiated on the loading phase of three intravitreal doses of 2 mg aflibercept in routine clinical practice were recruited from December 2019 to August 2021. The response to the loading phase was assessed at approximately 8 weeks post-loading (up to 140 days from first injection) based on different definitions of response. The proportion of patients that qualify for interval extension based on different clinical trial criteria was also evaluated. RESULTS: A total of 722 patients with visual acuity (VA) and optical coherence tomography (OCT) scans done at all 4 visits were included. Of these 32.4% of eyes responded with complete macular fluid resolution after the first injection with no recurrence through the loading phase (super-responders) while 26.9% had persistent macular fluid in all 4 visits (true non-responders). The rest were considered suboptimal responders. Change in VA showed marked variations within each of these categories of fluid resolution. For extension of next treatment interval, if presence of any macular fluid at the post-loading visit is the only criteria considered, about 50% could be extended to 8 weeks. If both VA worsening by ≥5 letters and a > 25 µm increase in central sub-field thickness (CST) are considered, 90% will be eligible for interval extension. CONCLUSION: Clinical trial designs and pre-defined treatment extension/shortening criteria determine the proportion of patients requiring treatment in the post-loading visit. The short and long-term impact of interval extension immediate post-loading on visual outcome in clinical practice is unknown.

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

Objective: Current cost-effectiveness analyses (CEA) emphasise 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 utilisation 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.

Subretinal transient hyporeflectivity in neovascular age-related macular degeneration and its response to a loading phase of aflibercept: PRECISE report 4.

PURPOSE: To describe the prevalence of subretinal transient hyporeflectivity (STHR) in exudative neovascular age-related macular degeneration (nAMD) and its response to a loading phase of aflibercept. METHODS: Optical coherence tomography (OCT) scans of treatment-naïve nAMD patients captured at baseline and after a loading phase of aflibercept were graded for presence of STHR, defined as a small, well-defined, round, subretinal, hyporeflective area, delimited between the ellipsoid zone (EZ) and the retinal pigmented epithelium/Bruch membrane complex. OCT parameters recorded were macular neovascularisation (MNV) subtypes, location of retinal fluids (subretinal fluid, SRF and intraretinal fluid, IRF), central retinal and choroidal thickness. Response was defined as absence of IRF and SRF. Factors associated with completely resolved STHR versus persistent STHR post-loading phase were compared. RESULTS: 2039 eyes of 1901 patients were analysed. STHR was observed in 79 eyes of 78 patients, with an estimated prevalence of 3.87% (95% CI 3.08-4.81%). STHR were seen in 44 type 1 MNV (56%), 27 with type 2 (34%), and 8 with type 3 (10%). At baseline, a total of 303 STHR were present, ranging between 1-22 per eye. The total number of STHR reduced significantly after the loading phase to 173 (p = 0.002). Complete disappearance of STHR was seen in 44 eyes (56%) and persistent STHR in the rest (44%). CONCLUSIONS: STHR may represent a marker of low-grade exudation in nAMD eyes with good response to a loading phase of aflibercept. However, its potential role as an independent nAMD activity biomarker is limited as most resolve after the loading phase.

Associations of presenting visual acuity with morphological changes on OCT in neovascular age-related macular degeneration: PRECISE Study Report 2.

PURPOSE: To study associations of optical coherence tomography (OCT) features with presenting visual acuity (VA) in treatment naive neovascular age-related macular degeneration (nAMD). METHODS: Patients with nAMD initiated on aflibercept therapy were recruited from December 2019 to August 2021. Demographic and OCT (Spectralis, Heidelberg Engineering) features associated with good VA (VA ≥ 68 ETDRS letters, Snellen ≥ 6/12) and poor VA (VA < 54 letters, Snellen < 6/18) were analysed using Generalised Estimating Equations to account for inter-eye correlation. RESULTS: Of 2274 eyes of 2128 patients enrolled, 2039 eyes of 1901 patients with complete data were analysed. Mean age was 79.4 (SD 7.8) years, female:male 3:2 and mean VA 58.0 (SD 14.5) letters. On multivariable analysis VA < 54 letters was associated with increased central subfield thickness (CST) (OR 1.40 per 100 µm; P < 0.001), foveal intraretinal fluid (OR 2.14; P < 0.001), polypoidal vasculopathy (PCV) relative to Type 1 macular neovascularisation (MNV) (OR 1.66; P = 0.049), presence of foveal subretinal hyperreflective material (SHRM) (OR 1.73; P = 0.002), foveal fibrosis (OR 3.85; P < 0.001), foveal atrophy (OR 5.54; P < 0.001), loss of integrity of the foveal ellipsoid zone (EZ) or external limiting membrane (ELM) relative to their preservation (OR 3.83; P < 0.001) and absence of subretinal drusenoid deposits (SDD) (presence vs absence; OR 0.75; P = 0.04). These features were associated with reduced odds of VA ≥ 68 letters except MNV subtypes and SDD. CONCLUSION: Presence of baseline fovea-involving atrophy, fibrosis, intraretinal fluid, SHRM, PCV EZ/ELM loss and increased CST determine poor presenting VA. This highlights the need for early detection and treatment prior to structural changes that worsen baseline VA.

Baseline characteristics of eyes with early residual fluid post loading phase of aflibercept therapy in neovascular AMD: PRECISE study report 3.

PURPOSE: To compare the baseline characteristics in patients with and without early residual fluid (ERF) after aflibercept loading phase (LP) in patients with treatment naïve neovascular age related macular degeneration (nAMD). METHODS: Patients with nAMD initiated on LP of three intravitreal aflibercept doses were recruited from December 2019 to August 2021. Baseline demographic and OCT features associated with any ERF were analysed using Generalised Estimating Equations to account for inter-eye correlation. Receiver operating characteristic (ROC) curve was performed for selection of CST threshold. RESULTS: Of 2128 patients enrolled, 1999 eyes of 1862 patients with complete data were included. After LP, ERF was present in 1000 (50.0%), eSRF in 746(37.3%) and eIRF in 428 (21.4%) eyes. In multivariable analysis of baseline features, eyes with increased central subfield thickness (CST) (OR 1.31 per 100 microns increase [95% CI 1.22 to 1.41]; P < 0.001), eyes with IRF and SRF at baseline (1.62 [95% CI 1.17 to 2.22]; P = 0.003), and those with SRF only (OR 2.26 [95% CI 1.59 to 3.20]; P < 0.001) relative to IRF only were determinants of ERF. CST ≥ 418 microns had 57% sensitivity and 58% specificity to distinguish ERF from no ERF at visit 4. CONCLUSION: On average, 50% of eyes have ERF after aflibercept LP. Clinically relevant baseline determinants of ERF include CST ≥ 418 µ and presence of only SRF. These eyes may require further monthly treatment before extending treatment intervals.

Outcomes of Treatment-Resistant Neovascular Age-Related Macular Degeneration Switched from Aflibercept to Faricimab.

PURPOSE: Although previous studies have demonstrated the efficacy of faricimab in treatment-naive patients with neovascular age-related macular degeneration (nAMD), its outcomes in patients switched from aflibercept are less understood. This study aimed to assess clinical anatomical and functional outcomes of switching to faricimab in patients undergoing aflibercept intravitreal injections (IVIs) for nAMD with suboptimal response. DESIGN: Retrospective case series. SUBJECTS: Patients with nAMD at a single tertiary care center who were switched from aflibercept to faricimab due to persistent suboptimal response. METHODS: Patients had received a minimum of 6 consecutive IVIs of aflibercept and showed persistent presence of intraretinal (IRF) or subretinal fluid (SRF) on OCT despite receiving aflibercept at 4 or 6-weekly intervals at the time of the switch. Patients receiving 4-weekly aflibercept were switched with either 2 or 3 loading doses of 4-weekly faricimab injections. Regression models were used to identify predictors of clinical outcomes. MAIN OUTCOME MEASURES: Visual acuity, central macular thickness (CMT), and OCT parameters were assessed preswitch and postswitch. RESULTS: Eighty-one eyes of 68 patients were included. The mean age was 79.1 years (standard deviation: 8.9), and females constituted 53% of cases. A statistically significant reduction in CMT was observed postswitch (P < 0.0001). The proportion of cases with IRF (P = 0.0219) and SRF (P < 0.000) decreased significantly. Overall clinical improvement on OCT was noted in 80% of patients. No significant improvement in ETDRS vision was observed. There was no evidence that switching regimen (2 vs. 3 loading doses) had an independent effect on clinical outcomes. CONCLUSION: Among patients with treatment-resistant nAMD, switching from aflibercept to faricimab may serve as a safe and effective option. Significant anatomical improvements were observed, with a trend toward visual stability. The loading regimen with 2 faricimab injections appeared to be sufficient for nonnaive patients. However, a longer follow-up and larger studies are warranted to confirm these findings. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Outer retinal corrugations in late-onset retinal degeneration: a diagnostic finding demonstrated with multimodal imaging.

OBJECTIVE: Late-onset retinal degeneration (L-ORD) is a rare autosomal dominant retinal degeneration that presents in the sixth decade and leads to severe visual loss. The objective of this paper is to describe outer retinal corrugations as a diagnostic feature of L-ORD. METHODS: This retrospective study reviewed consecutive patients diagnosed with L-ORD, confirmed through complete ophthalmic examination, multimodal imaging and genetic tests. Multimodal imaging investigations included spectral domain-optical coherence tomography (SD-OCT) and ultra-wide-field colour and autofluorescence fundus photographs. RESULTS: A total of 13 eyes of 9 patients with L-ORD had outer retinal corrugations identified on OCT scans. CONCLUSION: Outer retinal corrugations may be a diagnostic finding for L-ORD. The detection of this sign may aid diagnosis and characterisation of this disease and help in the differential diagnosis with other acquired pathologies.

A Multi-Modal AI-Driven Cohort Selection Tool to Predict Suboptimal Non-Responders to Aflibercept Loading-Phase for Neovascular Age-Related Macular Degeneration: PRECISE Study Report 1.

Patients diagnosed with exudative neovascular age-related macular degeneration are commonly treated with anti-vascular endothelial growth factor (anti-VEGF) agents. However, response to treatment is heterogeneous, without a clinical explanation. Predicting suboptimal response at baseline will enable more efficient clinical trial designs for novel, future interventions and facilitate individualised therapies. In this multicentre study, we trained a multi-modal artificial intelligence (AI) system to identify suboptimal responders to the loading-phase of the anti-VEGF agent aflibercept from baseline characteristics. We collected clinical features and optical coherence tomography scans from 1720 eyes of 1612 patients between 2019 and 2021. We evaluated our AI system as a patient selection method by emulating hypothetical clinical trials of different sizes based on our test set. Our method detected up to 57.6% more suboptimal responders than random selection, and up to 24.2% more than any alternative selection criteria tested. Applying this method to the entry process of candidates into randomised controlled trials may contribute to the success of such trials and further inform personalised care.

Evaluation of care with intravitreal aflibercept treatment for UK patients with diabetic macular oedema: DRAKO study 24-month real-world outcomes.

BACKGROUND/ OBJECTIVES: DRAKO (NCT02850263) was a 24-month, prospective, observational, multi-centre cohort study that enrolled patients diagnosed with diabetic macular oedema (DMO) including central involvement. The study aimed to evaluate standard of care intravitreal aflibercept (IVT-AFL) treatment in the UK. This analysis describes the 12-month outcomes for patients with prior anti-vascular endothelial growth factor (VEGF) treatment for DMO other than IVT-AFL (C2), and 2-year outcomes for both anti-VEGF treatment-naïve patients (C1) and C2 patients. METHODS: Study eyes were treated with IVT-AFL as per local standard of care. Mean changes in best-corrected visual acuity (BCVA) in ETDRS letters and central subfield thickness (CST) were stratified by baseline factors. Changes in diabetic retinopathy assessments, glycated haemoglobin A1c levels and vision-related quality of life (QoL) were evaluated alongside numbers of injections administered and safety outcomes. RESULTS: For C1, mean (SD) changes from baseline in BCVA of +0.7 (12.7) letters and CST of -123.3 (104.3) µm were observed at Month 24. For C2, mean (SD) changes from baseline for BCVA of + 0.2 (10.2) letters and -0.3 (13.0) letters, and CST of -79.1 (137.6) µm and -91.6 (132.9) µm, were observed at 12 and 24 months, respectively. In Year 2, C1 and C2 patients received a mean of 3.7 and 4.3 injections, respectively. CONCLUSIONS: Year 2 results indicate that IVT-AFL is an effective treatment for DMO in real-world UK clinical practice, despite relatively low injection numbers. The high baseline visual acuity and QoL scores were maintained and there was further improvement in anatomical outcomes.

Evaluation of standard-of-care intravitreal aflibercept treatment practices in patients with diabetic macular oedema in the UK: DRAKO study outcomes.

BACKGROUND/OBJECTIVES: DRAKO (NCT02850263) was a 24-month, prospective, non-interventional, multi-centre cohort study enrolling patients with diabetic macular oedema (DMO) including central involvement. The study evaluated UK standard-of-care intravitreal aflibercept (IVT-AFL) treatment. This analysis describes the treatment pathway and service provision for the anti-vascular endothelial growth factor (VEGF) treatment-naïve (C1) and non-naïve patients (C2) who received prior anti-VEGF treatment for DMO other than IVT-AFL. METHODS: Mean changes in best-corrected visual acuity and central subfield thickness were measured and stratified by baseline factors, including ethnicity and administration of five initial monthly injections within predefined windows. Clinic visits were classified as treatment only (T1), monitoring assessment only (T2), combined visits (T3) or post-injection visits with no treatment or assessment (T4). RESULTS: Median time from decision to treat to treatment was 6 days. As a percentage of total visits, T1, T2, T3 and T4 were 7%, 42%, 48% and 3% for C1 and 11%, 39%, 48% and 2% for C2. Most IVT-AFL injections were administered by healthcare professionals (HCPs) other than doctors (C1, 57.4%; C2, 58.5%). The percentage of treatments associated with a procedure-related adverse event where at least 75% of injections were completed by the same injector role were similar for doctors and other HCPs (C1, 1.1% and 0.8%; C2, 0.7%, and 1.0%). CONCLUSIONS: Results indicate that upon DMO diagnosis, patients were treated promptly, and most visits were combined (treatment and assessment) or monitoring only. Most IVT-AFL was administered by non-physicians with a similar treatment-related safety profile as IVT-AFL administered by physicians.

The Danger of Laser Pointer-Induced Retinal Damage in Children: A Large United Kingdom Case Series and Survey of Public Awareness.

PURPOSE: To explore the clinical features of laser pointer-related retinal injuries among children and gain insight into the general public awareness around laser pointer use. METHODS: This was a retrospective case series of 9 children (12 eyes) with laser pointer-related retinal injury from a United Kingdom tertiary ophthalmology unit and a prospective survey of laser pointer use and awareness among children and parents presenting to the hospital eye service for other eye conditions. RESULTS: Within the case series, 67% of patients were asymptomatic on presentation. A mean follow-up of 25.6 months showed that structural changes persisted in all cases, and in one case, there was progression in the macular lesion size. One case presented with secondary choroidal neovascular membrane, requiring intravitreal anti-vascular endothelial growth factor injections. A survey showed that 9% of children admitted to having played with laser pointers and 13% of parents were aware of their children playing with laser pointers. Only one-third of children and parents were aware of laws regulating laser pointers. Most parents (96%) agreed that there needs to be increased awareness regarding laser pointers' effect on vision. CONCLUSIONS: This study has highlighted that although children may be asymptomatic at presentation, there is usually permanent structural damage to the macula, and complications such as secondary choroidal neovascular membrane can develop years later. The survey found a relatively high incidence of laser pointer use with little awareness of the regulation laws. There is an urgent need to establish more robust measures to improve public awareness and regulations around laser pointers. [J Pediatr Ophthalmol Strabismus. 2023;60(1):52-59.].

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.

Evaluation of standard of care intravitreal aflibercept treatment of diabetic macular oedema treatment-naive patients in the UK: DRAKO study 12-month outcomes.

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.

Desferrioxamine-Related Pseudo-Vitelliform Dystrophy and the Effect of Anti-Vascular Endothelial Growth Factor.

We report a case of a 72-year-old female who developed bilateral pseudo-vitelliform dystrophy after taking desferrioxamine for the treatment of chronic iron overload. The patient then developed a right superior hemiretinal vein occlusion associated with intraretinal fluid in the right eye and was treated with monthly intravitreal aflibercept injections for 3 months followed by as required treatment. In addition to the intraretinal fluid responding to anti-VEGF treatment, there was a reduction in the size of the pseudo-vitelliform subfoveal deposit height, which was not seen in the untreated eye. Our case of an uncommon presentation of desferrioxamine-related maculopathy associated with a vein occlusion and the changes associated with intravitreal anti-VEGF treatment may help with the potential hypotheses of the pathophysiology of desferrioxamine-related pseudo-vitelliform retinal lesions and help with the potential future treatments of the condition.

Two years' experience of screening for hydroxychloroquine retinopathy.

BACKGROUND: The Royal College of Ophthalmologists (RCOphth) recently produced new guidelines for the screening of hydroxychloroquine (HCQ) retinopathy. New imaging techniques have suggested an increased prevalence of retinopathy (7.5%) compared with previous studies (0.5%). METHODS: We collected prospective data from all patients referred to Sunderland Eye Infirmary, Sunderland for HCQ screening. Patients were screened according to RCOphth guidelines. In addition to retinal images, the data recorded included visual acuity, visual fields and multifocal electroretinography as appropriate, the patient's age, diagnosis, weight, renal function and use of tamoxifen. RESULTS: Of the 678 patients screened, 333 were categorised to be at risk (251 patients had been on HCQ >5 years, 117 had an estimated glomerular function rate <60 ml/min/1.73 m2, and 46 were on a dose >5 mg/kg/day). Eighty patients had multiple risk factors, 31 had been on doses of >5 mg/kg/day for >5 years. One hundred and sixty-eight of these patients have now been screened twice. The prevalence of HCQ retinopathy was 2/678 (0.3%) of all screened, 2/333 (0.6%) of patients at risk. CONCLUSIONS: Our results show a far lower rate of retinopathy compared to the widely reported figure taken as standard by the RCOphth. This may be multifactorial: this prospective analysis has fewer patients taking higher doses of HCQ and shorter follow up, the comparison of serial images may highlight more cases and in addition, there are significant numbers of patients yet to be referred. Finally, the RCOphth's diagnostic criteria is more exacting than that of the recent literature.

Recommendations by a UK expert panel on an aflibercept treat-and-extend pathway for the treatment of neovascular age-related macular degeneration.

OBJECTIVES: This report aims to provide clear recommendations and practical guidance from a panel of UK retinal experts on an aflibercept treat-and-extend (T&E) pathway that can be implemented in clinical practice. These recommendations may help service providers across the NHS intending to implement a T&E approach, with the aim of effectively addressing the capacity and resource issues putting strain on UK neovascular age-related macular degeneration (nAMD) services while promoting patients' best interests throughout. METHODS: Two structured roundtable meetings of retinal specialists were held in London, UK on 7 December 2018 and 1 March 2019. These meetings were organised and funded by Bayer. RESULTS: The panel provided recommendations for an aflibercept T&E pathway and developed specific criteria based on visual acuity, retinal morphology and optical coherence tomography imaging to guide reduction, maintenance and extension of injection intervals. They also discussed the extension of treatment intervals by 2- or 4-week adjustments to a maximum treatment interval of 16 weeks, the management of retinal fluid and the stopping of treatment. CONCLUSIONS: The long-term benefits of implementing a T&E pathway may include superior visual outcomes compared with a pro re nata (PRN; as needed) protocol, and a lower treatment burden compared with a fixed protocol, which is likely to improve service capacity. Furthermore, the predictable nature of a T&E approach compared with a PRN service may aid capacity planning for the future nAMD treatment demand.

Acute Chemical Eye Injury and Limbal Stem Cell Deficiency-A Prospective Study in the United Kingdom.

PURPOSE: To analyze the incidence, nature, outcomes, and complications of acute chemical eye injuries, including the incidence of limbal stem cell deficiency (LSCD) and to compare the 2 main classifications for ocular chemical injuries: Roper-Hall (RH) and Dua. METHODS: This is a prospective, consecutive, interventional single-center study between April and October 2009 of all new patients with acute chemical eye injury presenting to the Royal Victoria Infirmary eye emergency department (EED). RESULTS: Of 11,683 patients who attended the EED, 98 patients (110 eyes) presented with acute chemical eye injury (60% male). This represents an estimated annual incidence of 5.6 new cases per 100,000 population. Mean age was 36.5 years (1-78; SD 17.1 years), including 7 children (age <10 years). Fifty-one patients (52%) had work-related injuries. The most common chemical agent was alkali (78%). All 4 RH grade IV cases were unilateral, assault with ammonia, and required early amniotic membrane transplantation as per the protocol, but despite full treatment, they developed total LSCD in the affected eye. CONCLUSIONS: Acute chemical eye injuries are rare. Male patients in the working age group are more prone to work-related chemical injuries, whereas young children tend to have domestic injuries. Grade I, II, and III RH and Dua chemical injuries had a very good prognosis with topical treatment only, whereas RH grade IV (Dua grade IV-VI), mainly assaults with ammonia, progressed to total/severe LSCD despite appropriate management including early amniotic membrane transplantation. The Dua classification includes conjunctival involvement, having a greater value in predicting the final clinical outcome when grading chemical eye injuries.

A long history of dense deposit disease.

BACKGROUND: Dense Deposit Disease is a rare condition affecting the Bruch's membrane and the glomerular basement membrane. We report the progression of the ocular manifestations over a 30 year follow up period, longer than any previous report. CASE PRESENTATION: A 44 year old male presented with pigmentary changes at the macula noted by his optician. Best corrected visual acuity at presentation was good in both eyes. Fundoscopy showed pigmentary changes and drusen, and investigation using intravenous fundus fluorescein angiography did not demonstrate any choroidal neovascular membrane. The patient subsequently developed renal failure and received a dual renal transplant. The transplanted kidneys also failed over the coming year. The patient's vision gradually deteriorated and comparison between the images in 2010 and 1985 demonstrated a clear progression of the macula changes. Optical coherence tomography showed multiple subretinal hyper reflective drusenoid deposits. These deposits were also noted to be autofluorescent on blue auto-fluorescence. The young age at presentation of drusen, combined with the history of recurrent kidney failure and progression of subretinal deposits led to a diagnosis of dense deposit disease. CONCLUSIONS: Dense deposit disease is a rare condition affecting Bruch's membrane, but should be considered in the differential diagnosis of any patient under the age of 50 years presenting with drusen.