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.

Action on neovascular age-related macular degeneration (nAMD): recommendations for management and service provision in the UK hospital eye service.

This report by a group of UK retina specialists and health professionals considers best practice recommendations for the management of sight-threatening neovascular age-related macular degeneration (nAMD), based on collective experience and expertise in routine clinical practice. The authors provide an update for ophthalmologists, allied healthcare professionals and commissioners on practice principles for optimal patient care and service provision standards. Refinement of care pathways for nAMD has improved access to intravitreal anti-vascular endothelial growth factor therapy but there are still variations in care and reported outcomes between clinic centres. Innovative organisational models of service provision allow providers to better match capacity with increasing demand. The authors review the recent NICE guideline for diagnosis and management of AMD, considerations for switching therapies and stopping treatment and need for regular monitoring of non-affected fellow eyes in patients with unilateral nAMD. Actions for delivery of high-quality care and to improve long-term patient outcomes are discussed. Local pathways need to detail nAMD target time to treat, maintenance of review intervals to ensure proactive treatment regimens are delivered on time and appropriate discharge for patients deemed low risk or no longer benefiting from treatment. Actual visual acuity outcomes achieved and maintenance of the level of vision when disease stability is achieved are considered good measures for judging the quality of care in the treatment of patients with nAMD. Robust community referral pathways must be in place for suspected reactivation of choroidal neovascularisation and rapid referral for second eye involvement. Practical considerations for intravitreal injection therapy are outlined.

Bevacizumab for treatment of choroidal neovascularization secondary to candida chorioretinitis.

PURPOSE: To report a case of juxtafoveal choroidal neovascularization in a patient with candida chorioretinitis successfully treated with intravitreal bevacizumab. METHODS: Case report. RESULTS: A 45-year-old woman previously treated for candida chorioretinitis was presented with reduced vision in the left eye. The patient was investigated with ophthalmoscopy, fluorescein angiography, and optical coherence tomography (OCT). Following initial treatment, fundus examination, fluorescein angiography, and OCT of the right eye revealed a secondary juxtafoveal classic choroidal neovascularization. Following a single intravitreal injection of bevacizumab, the patient had excellent visual recovery, with absence of subretinal or intraretinal fluid in the OCT. CONCLUSIONS: Bevacizumab was effective in treatment of choroidal neovascularization associated with candida chorioretinitis.

Aflibercept treatment for neovascular AMD beyond the first year: consensus recommendations by a UK expert roundtable panel, 2017 update.

National recommendations on continued administration of aflibercept solution for injection after the first year of treatment for neovascular age-related macular degeneration (nAMD) have been developed by an expert panel of UK retina specialists, based on clinician experience and treatment outcomes seen in year 2. The 2017 update reiterates that the treatment goal is to maintain or improve the macular structural and functional gains achieved in year 1 while attempting to reduce or minimize the treatment burden, recognizing the need for ongoing treatment. At the end of year 1 (ie, the decision visit at month 11), two treatment options should be considered: do not extend the treatment interval and maintain fixed 8-weekly dosing, or extend the treatment interval using a treat-and-extend regimen up to a maximum 12 weeks. Criteria for considering not extending the treatment interval are persistent macular fluid with stable vision, recurrent fluid, decrease in vision in the presence of fluid, macular hemorrhage, new choroidal neovascularization or any other sign(s) of exudative disease activity considered vision threatening in the opinion of the treating clinician. Treatment extension is recommended for eyes with a dry macula (ie, without macular fluid) and stable vision. Under both options, the treatment interval may be shortened if visual and/or anatomic outcomes deteriorate. Monitoring without treatment may be considered for eyes with a fluid-free macula for a minimum duration of 48 weeks. A patient completing one full year of monitoring without requiring injections may be considered for discharge from clinic. The treatment algorithm incorporates return to fixed 8-weekly dosing for disease reactivation during treatment extension and reinstatement of treatment for disease recurrence following discontinuation or discharge. For bilateral nAMD, either the eye requiring the more intensive treatment or the eye with the better vision, guided by local clinical practice, should determine the retreatment schedule overall.

Multimodal Imaging in Acute Posterior Multifocal Placoid Pigment Epitheliopathy Demonstrating Obstruction of the Choriocapillaris.

Optical coherence tomography angiography (OCTA) provides noninvasive in vivo vascular imaging of the retina and choriocapillaris. To highlight OCTA utility, the authors align structural changes and their resolution with functional outcome. The authors present a case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and sequential changes during transition to inactive disease. In the acute phase, altered flow and nonperfusion were seen in defined islands of choriocapillaris. Over time, progressive reperfusion was observed and accompanied clinical resolution and functional visual restoration. The imaging features acquired described the level of nonperfusion the authors had assumed when extrapolating findings from multiple independent imaging modalities. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:677-681.].

Managing juvenile idiopathic arthritis-associated uveitis.

Bilateral chronic anterior uveitis is an extra-articular feature of juvenile idiopathic arthritis. Although figures vary, uveitis occurs in approximately 11%-13% of patients with this disease and is most commonly associated with the female gender, oligoarthritis, and presence of antinuclear antibodies. The disease has an insidious onset and is often asymptomatic. Managing patients with juvenile idiopathic arthritis-associated uveitis remains challenging as the disease may prove to be refractory to traditional treatment regimens. Stepwise immunomodulatory therapy is indicated, with new biologic drugs being used last in cases of refractory uveitis. Small scale studies and practice have provided the evidence to undertake randomized control trials to evaluate the efficacy, safety, and cost-effectiveness of anti-tumor necrosis factor-α therapies, such as infliximab and adalimumab. These have demonstrated promising results, with further data awaited from ongoing trials for adalimumab (as SYCAMORE and ADJUVITE trials). Lower grade evidence is supporting the use of newer biologics such as rituximab, daclizumab, tocilizumab, and abatacept in those cases refractory to anti-tumor necrosis factor-α therapy.

Phase IIb clinical trial of ranibizumab for the treatment of uveitic and idiopathic choroidal neovascular membranes.

AIM: To assess the efficacy of intravitreal ranibizumab for the treatment of new onset inflammatory choroidal neovascularisation (iCNV), including both uveitic and idiopathic CNVs. METHODS: Single-centre, open-label, non-randomised Phase IIb clinical trial. Patients fulfilling strict entry criteria of new onset iCNV were given monthly intravitreal ranibizumab injections for 3 months. Thereafter, re-treatment was based on evidence of persisting activity. All patients completed trial follow-up. Optical coherence tomography (OCT) and best-corrected visual acuity (BCVA) were performed at every visit. Fluorescein angiography was performed at baseline, months 4 and 12. Descriptive analysis and Wilcoxon non-parametric test were performed for analysis. RESULTS: 15 patients, 10 women with a mean age of 48.8 years (range 24-85 years) were included in the study. The mean number of injections was 4.33 (range 3-7). There was a statistically significant difference in the BCVA at month 4 (p=0.001) and at month 12 (p=0.001) compared with baseline. The mean gain in BCVA at month 4 compared with baseline was 20±15.36 letters (mean±SD), and at month 12 was 21±16.97 letters. There was a statistically significant difference in the mean central subfield thickness (CST) at baseline versus month 4 (p=0.003) and month 12 (p=0.001). CONCLUSION: Patients gained vision (mean of 21 letters at 12 months) and showed reduced CST. These results support the continued use of ranibizumab in the treatment of iCNV. TRIAL REGISTRATION NUMBER: 2008-007476-19, results.

Localized choroidal thickness variation and pigment epithelial detachment in dome-shaped macula with subretinal fluid.

The objective of this report is to demonstrate that individuals with dome-shaped macula can develop persistent subretinal fluid due to abrupt changes in the thickness of the choroid, making it unlikely to be reported. Additionally, these patients often have pigment epithelial detachments, suggestive of possible choroidal neo-vascularization. These two qualities can often lead to persistent subretinal fluid that is refractory to treatment.

Multicenter study of intravitreal dexamethasone implant in noninfectious uveitis: indications, outcomes, and reinjection frequency.

PURPOSE: To identify clinical outcomes and treatment patterns of intravitreal dexamethasone implant (Ozurdex; Allergan, Inc) in noninfectious uveitis in the clinical setting. DESIGN: Multicenter retrospective cohort study. METHODS: Eighty-two eyes (63 patients) receiving 142 implant injections over 35 months were included. Treatment indication, uveitis diagnosis, visual acuity, intraocular pressure, vitreous haze score, central retinal thickness by optical coherence tomography, phakic status, number of injections, time to reinjection, systemic treatments, and complications data were collected. Time to visual acuity and vitreous haze score improvement as per the Standardization of Uveitis Nomenclature guidelines were also determined. RESULTS: The probability of visual acuity improvement (≥0.3 logarithm of the minimal angle of resolution units improvement) was 39% at 1 month, 49% at 3 months, 52% at 6 months, and 58% at 12 months. Eyes with baseline vitritis (vitreous haze score ≥+0.5, n = 45) had a probability of vitreous haze score improvement (2-step decrease or change from +0.5 to 0) at 2 weeks of 41%, at 1 month 63%, at 3 months 73%, at 6 months 79%, and at 12 months 88%. In eyes that completed 12-month follow-up (n = 54), 40.7% underwent 2 injections (mean time to second injection of 6.6 ± 1.9 months) and 11.2% required ≥3 injections (mean time to third injection of 11 ± 1.5 months). CONCLUSIONS: Dexamethasone implant use in uveitis provides favorable visual acuity and vitreous haze score outcomes but requires repeated injections, an important consideration when choosing intraocular treatment as a route to controlling uveitis.

Management of upper eyelid cicatricial entropion.

PURPOSE: There is a paucity of published data on the management of upper eyelid cicatricial entropion. We report on our results using such techniques as lamella repositioning, recession or augmentation and terminal tarsal rotation. DESIGN: Observational retrospective case series. PARTICIPANTS: Consecutive cases of upper eyelid cicatricial entropion of two specialist oculoplastic centres (Corneoplastic Unit, East Grinstead, UK and South Australian Institute of Ophthalmology, Adelaide, Australia) were reviewed over a 7-year period. METHODS: All patients underwent anterior lamellar repositioning or terminal tarsal rotation. MAIN OUTCOME MEASURES: Success was defined by two definitions: anatomical success was defined where the lid margin was restored to its normal position. Complete success was defined where there were no eyelashes touching the globe. Gain or loss (≤ or ≥2 Snellen lines) in best corrected visual acuity using a Snellen chart and resolution of any corneal epitheliopathy at final follow-up were also recorded (as graded by experienced oculoplastic consultants). RESULTS: Fifty-two procedures were performed on 41 patients (11 bilateral). All patients underwent either an anterior lamellar repositioning or a terminal tarsal rotation. Trachoma, previous upper lid surgery, Stevens-Johnson syndrome and meibomian gland dysfunction were the commonest underlying diagnoses. Ninety-eight per cent of the group had a normal anatomical lid position at follow-up. Nine eyelids (17%) of the group had recurrence of trichiasis. CONCLUSION: This large case series demonstrates that upper eyelid cicatricial entropion is managed effectively utilizing procedures that involve recession and reposition. We recommend that excision of tissue is avoided, especially in pathology that has a progressive immunological cicatricial drive.

Review and update of central serous chorioretinopathy.

PURPOSE OF REVIEW: Greater understanding of central serous chorioretinopathy (CSCR) has changed initial beliefs that CSCR is a benign condition affecting young men with almost complete resolution. CSCR has a spectrum of presentations with more diffuse retinal dysfunction and variations between races. CSCR can affect older individuals and in a subset of patients may lead to significant ocular morbidity. RECENT FINDINGS: Advances in imaging, particularly in indocyanine green angiography and optical coherence tomography, have led to a greater understanding of the pathophysiology of this condition. Treatments for CSCR are still evolving, in particular photodynamic dynamic therapy using lower doses and reduced fluence showing promising results. More research is required on ideal dosage. Anti-vascular endothelial growth factor treatment offers a new medical treatment modality with promising results. SUMMARY: There have been recent imaging developments in addition to therapeutic advances for refractory CSCR.

Analysis of the diurnal intraocular pressure profile pre and post trabeculectomy using 24-hour monitoring of intraocular pressure.

PURPOSE: To compare the diurnal intraocular pressure (IOP) profile pre and post trabeculectomy with a control group of medically controlled patients. We compared the change in mean, peak, and diurnal IOP fluctuation. METHODS: This was an observational study of patients at the Bristol Eye Hospital, United Kingdom. All patients underwent initial and subsequent phasing, with surgery between for cases. The unpaired Student t test compared the changes (initial-subsequent) in mean, peak, and fluctuation between cases and controls. RESULTS: Fifteen eyes underwent trabeculectomy surgery while the control group contained 17 eyes controlled on topical medical treatment. There was a statistically significant reduction in both mean IOP of 3.7 mmHg (p=0.002) and peak IOP of 4.4 mmHg (p=0.025) in the surgical group compared to the medical group. There was no statistically significant change in the IOP fluctuation between the 2 study groups (p=0.296). CONCLUSIONS: There is a significant reduction in mean IOP and peak IOP following trabeculectomy. We showed no statistically significant change in the diurnal fluctuation of IOP following trabeculectomy.

Review and update of involuntary facial movement disorders presenting in the ophthalmological setting.

We review the existing literature on the involuntary facial movement disorders-benign essential blepharospasm, apraxia of eyelid opening, hemifacial spasm, and aberrant facial nerve regeneration. The etiology of idiopathic blepharospasm, a disorder of the central nervous system, and hemifacial spasm, a condition involving the facial nerve of the peripheral nervous system, is markedly different. We discuss established methods of managing patients and highlight new approaches.

The management of diabetic macular oedema.

Diabetic macular oedema (DMO) is a significant cause of visual loss in the working population. Focal/grid photocoagulation remains an effective treatment for DMO and the benchmark to which clinicians compare other newer treatment modalities. There are, however, patients who do not respond adequately or who are refractory to laser photocoagulation. This has led to the development of newer treatments such as the intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors as well as intravitreal corticosteroid releasing delivery systems. Cataract formation and raised intraocular pressure remain the major disadvantages of corticosteroid use. There is mounting evidence that intravitreal VEGF inhibitors with or without combined laser photocoagulation will become the gold standard treatment for DMO.

Long-term orbitofacial complications of polyalkylimide 4% (bio-alcamid).

PURPOSE: To review our experience with the long-term orbitofacial complications of polyalkylimide 4% (Bio-Alcamid), including migration, infection, and recurrent swelling. METHODS: A retrospective case series of 4 patients who received preperiosteal polyalkylimide 4% filler treatment: 3 patients received treatment to cheeks and/or nasolabial folds and 1 received treatment to the tear-trough region. All 4 patients were referred with delayed complications. RESULTS: Four patients presented with the unusual delayed complications of infection including abscess formation, migration of filler, recurrent swelling, and inflammatory nodules. CONCLUSIONS: Because of the hydrophilic and endoprosthetic nature of polyalkylimide 4%, migration of the product is unexpected. We hypothesise that in our patients, filler migration occurred after bimanual expression and/or manipulation of the product with disruption of the surrounding collagen capsule. Because removal of polyalkylimide 4% is only achieved via aspiration and bimanual expression, which itself may precipitate long-term migration of the product, it is vital that clinicians are mindful of these complications and the pitfalls of overfill and misplacement of the product, for informed patient consent.

Long-term topical steroid treatment after penetrating keratoplasty in patients with pseudophakic bullous keratopathy.

PURPOSE: To assess the use of long-term topical corticosteroid treatment in patients with pseudophakic bullous keratopathy (PBK) after penetrating keratoplasty (PK). DESIGN: Retrospective cohort study. PARTICIPANTS: This study considered patients with PBK undergoing an initial PK procedure for visual reasons in the United Kingdom between April 1999 and March 2004. There were 1274 initial PK procedures for PBK reported to United Kingdom Transplant in this period, of which 1184 (91%) were grafted for visual reasons. Of these 1184 grafts, follow-up was reported in 1033 instances (87%). METHODS: A Cox regression model was used to investigate the combined effects of all preoperative factors (recipient age, human leukocyte antigen [HLA] matching, trephine size, deep stromal vascularization, surgeon activity) on graft failure. The model was fitted using all preoperative factors first, and subsequently, factors associated with corticosteroid and other medications were included. MAIN OUTCOME MEASURES: Graft survival. RESULTS: Three-year survival of grafts for PBK was 65% (95% confidence interval [CI], 59%-70%). Topical corticosteroids were still being used beyond 18 months after surgery in 378 (37%) of the 1033 corneal grafts included in this study. The grafts of patients not currently receiving steroids were 1.5 times as likely to fail (hazard ratio [HR], 1.5; 95% CI, 1.0-2.2; P<0.03). Lack of HLA matching (P = 0.006), trephine size or=8.00 mm (P = 0.03), recipient age younger than 65 years (P = 0.003), and corneal vascularization (P = 0.04) all increased the risk of graft failure. CONCLUSIONS: The use of long-term postoperative corticosteroids improved graft survival after PK for PBK. Barring patient contraindications for long-term topical corticosteroid use, clinicians should consider maintaining patients with PBK on long-term postoperative corticosteroid maintenance.

Delayed choroidal hemorrhage with concomitant subconjunctival hemorrhage after retinal detachment surgery.

BACKGROUND: Suprachoroidal hemorrhage is a known serious complication of all types of intraocular surgery and is associated with severe visual debility. Most cases of suprachoroidal hemorrhage occur intraoperatively. Suprachoroidal hemorrhage as a complication of vitrectomy has been described near the end of vitrectomy or on the first postoperative day. METHODS: This case report describes a patient presenting with a delayed suprachoroidal hemorrhage occurring 5 days after vitreoretinal surgery in association with subconjunctival hemorrhage. RESULTS AND CONCLUSION: To our knowledge, we report the first case of a delayed suprachoroidal hemorrhage associated with vitreoretinal surgery. With proper management, the outcome is not always unfavorable.