UNITED KINGDOM DATABASE STUDY OF INTRAVITREAL DEXAMETHASONE IMPLANT (OZURDEX) FOR MACULAR EDEMA RELATED TO RETINAL VEIN OCCLUSION.

PURPOSE: To study the treatment patterns, visual outcomes and safety profile of intravitreal dexamethasone implant (IDI) used for the treatment of macular edema secondary to retinal vein occlusion. METHODS: Up to 2 years of routinely collected anonymized data within electronic medical record systems were remotely extracted from 16 centers. The outcome measures include visual outcome, number of injections, and safety measures, including the rate of intraocular pressure (IOP) rise, frequency of IOP-lowering medication usage, and cataract surgery rates. RESULTS: The study included 688 eyes (44.4%) with central retinal vein occlusion and 862 eyes (55.6%) with branch retinal vein occlusion; 1,250 eyes (80.6%) were treatment naive and 28% (275/989) had high IOP or were on IOP-lowering medications before IDI use. It was found that 31% (476) of eyes received two injections, and 11.7% (182) and 3.7% (58) of eyes received three and four injections, respectively. The mean baseline Snellen visual acuity improved from 20/125 to 20/40 after the first injection. The probability of cataract surgery was 15% at 24 months. The proportion of eyes with ≥10 mmHg change from baseline was higher in phakic (14.2%) compared with pseudophakic eyes (5.4%, P = 0.004). Three eyes required IOP filtering surgery (0.2%). CONCLUSION: The visual results of IDI in eyes with macular edema secondary to retinal vein occlusion in the real world are comparable to those of clinical trial setting. Increased IOP in eyes with preexisting ocular hypertension or glaucoma can be controlled with additional medical treatment. Intraocular pressure rise with IDI may be more frequent in phakic than in pseudophakic eyes.

United Kingdom Diabetic Retinopathy Electronic Medical Record (UK DR EMR) Users Group: report 4, real-world data on the impact of deprivation on the presentation of diabetic eye disease at hospital services.

AIM: To assess the impact of deprivation on diabetic retinopathy presentation and related treatment interventions, as observed within the UK hospital eye service. METHODS: This is a multicentre, national diabetic retinopathy database study with anonymised data extraction across 22 centres from an electronic medical record system. The following were the inclusion criteria: all patients with diabetes and a recorded, structured diabetic retinopathy grade. The minimum data set included, for baseline, age and Index of Multiple Deprivation, based on residential postcode; and for all time points, visual acuity, ETDRS grading of retinopathy and maculopathy, and interventions (laser, intravitreal therapies and surgery). The main  outcome measures were (1) visual acuity and binocular visual state, and (2) presence of sight-threatening complications and need for early treatment. RESULTS: 79 775 patients met the inclusion criteria. Deprivation was associated with later presentation in patients with diabetic eye disease: the OR of being sight-impaired at entry into the hospital eye service (defined as 6/18 to better than 3/60 in the better seeing eye) was 1.29 (95% CI 1.20 to 1.39) for the most deprived decile vs 0.77 (95% CI 0.70 to 0.86) for the least deprived decile; the OR for being severely sight-impaired (3/60 or worse in the better seeing eye) was 1.17 (95% CI 0.90 to 1.55) for the most deprived decile vs 0.88 (95% CI 0.61 to 1.27) for the least deprived decile (reference=fifth decile in all cases). There is also variation in sight-threatening complications at presentation and treatment undertaken: the least deprived deciles had lower chance of having a tractional retinal detachment (OR=0.48 and 0.58 for deciles 9 and 10, 95% CI 0.24 to 0.90 and 0.29 to 1.09, respectively); in terms of accessing treatment, the rate of having a vitrectomy was lowest in the most deprived cohort (OR=0.34, 95% CI 0.19 to 0.58). CONCLUSIONS: This large real-world study suggests that first presentation at a hospital eye clinic with visual loss or sight-threatening diabetic eye disease is associated with deprivation. These initial hospital visits represent the first opportunities to receive treatment and to formally engage with support services. Such patients are more likely to be sight-impaired or severely sight-impaired at presentation, and may need additional resources to engage with the hospital eye services over complex treatment schedules.

Dexamethasone Intravitreal Implant Therapy for Retinal Vein Occlusion Macular Oedema and Conversion to Ranibizumab in Clinical Practice.

PURPOSE: Evaluation of outcomes in retinal vein occlusions (RVOs) for: (1) multiple repeat dexamethasone (DEX) injections and (2) conversion from DEX to ranibizumab. METHODS: We conducted a retrospective study evaluating outcomes of multiple DEX injections and those requiring conversion to ranibizumab at Moorfields Eye Hospital, Bedford, UK. All patients had undergone a complete ophthalmic work-up. RESULTS: Patients (n = 129) had a mean follow-up of 19.9 months. The mean improvement in central retinal thickness was 312 µm after final DEX (p = <0.0001). Mean peak best corrected visual acuity (BCVA) after final DEX was an improvement of 16 ETDRS letters (p < 0.0001). Forty-nine patients were converted and received a mean of 9.37 ranibizumab injections with a mean improvement in BCVA of 15 ETDRS letters (p < 0.0001) compared with final DEX. CONCLUSIONS: This study supports the use of ranibizumab in eyes previously treated with DEX and provides long-term efficacy and safety data for multiple DEX injection.

The United Kingdom Diabetic Retinopathy Electronic Medical Record Users Group: Report 3: Baseline Retinopathy and Clinical Features Predict Progression of Diabetic Retinopathy.

PURPOSE: To determine the time and risk factors for developing proliferative diabetic retinopathy (PDR) and vitreous hemorrhage (VH). DESIGN: Multicenter, national cohort study. METHODS: Anonymized data of 50 254 patient eyes with diabetes mellitus at 19 UK hospital eye services were extracted at the initial and follow-up visits between 2007 and 2014. Time to progression of PDR and VH were calculated with Cox regression after stratifying by baseline diabetic retinopathy (DR) severity and adjusting for age, sex, race, and starting visual acuity. RESULTS: Progression to PDR in 5 years differed by baseline DR: no DR (2.2%), mild (13.0%), moderate (27.2%), severe nonproliferative diabetic retinopathy (NPDR) (45.5%). Similarly, 5-year progression to VH varied by baseline DR: no DR (1.1%), mild (2.9%), moderate (7.3%), severe NPDR (9.8%). Compared with no DR, the patient eyes that presented with mild, moderate, and severe NPDR were 6.71, 14.80, and 28.19 times more likely to develop PDR, respectively. In comparison to no DR, the eyes with mild, moderate, and severe NPDR were 2.56, 5.60, and 7.29 times more likely to develop VH, respectively. In severe NPDR, the eyes with intraretinal microvascular abnormalities (IRMA) had a significantly increased hazard ratio (HR) of developing PDR (HR 1.77, 95% confidence interval [CI] 1.25-2.49, P = .0013) compared with those with venous beading, whereas those with 4-quadrant dot-blot hemorrhages (4Q DBH) had 3.84 higher HR of developing VH (95% CI 1.39-10.62, P = .0095). CONCLUSIONS: Baseline severities and features of initial DR are prognostic for PDR development. IRMA increases risk of PDR whereas 4Q DBH increases risk of VH.

The UK Diabetic Retinopathy Electronic Medical Record (UK DR EMR) Users Group, Report 2: real-world data for the impact of cataract surgery on diabetic macular oedema.

AIM: To assess the rate of 'treatment-requiring diabetic macular oedema (DMO)' in eyes for the two years before and after cataract surgery. METHODS: Multicentre national diabetic retinopathy (DR) database study with anonymised data extraction across 19 centres from an electronic medical record system. INCLUSION CRITERIA: eyes undergoing cataract surgery in patients with diabetes with no history of DMO prior to study start. The minimum dataset included: age, visual acuity (all time-points), injection episodes, timing of cataract surgery and ETDRS grading of retinopathy and maculopathy. MAIN OUTCOME MEASURE: rate of developing first episode of treatment-requiring DMO in relation to timing of cataract surgery in the same eye. RESULTS: 4850 eyes met the inclusion criteria. The rate of developing treatment-requiring DMO in this cohort was 2.9% in the year prior to surgery versus 5.3% in the year after surgery (p<0.01). The risk of 'treatment-requiring DMO' increased sharply after surgery, peaking in the 3-6 months' period (annualised rates of 5.2%, 6.8%, 5.6% and 4.0% for the 0-3, 3-6, 6-9 and 9-12 months' post-operative time periods respectively). Risk was associated with pre-operative grade of retinopathy: risk of DMO in the first year post-operatively being 1.0% (no DR pre-operatively), 5.4% (mild non-proliferative diabetic retinopathy; NPDR), 10.0% (moderate NPDR), 13.1% (severe NPDR) and 4.9% (PDR) (p<0.01). CONCLUSIONS: This large real-world study demonstrates that the rate of developing treatment-requiring DMO increases sharply in the year after cataract surgery for all grades of retinopathy, peaking in the 3-6 months' postoperative period. Patients with moderate and severe NPDR are at particularly high risk.

The United Kingdom Diabetic Retinopathy Electronic Medical Record Users Group, Report 1: baseline characteristics and visual acuity outcomes in eyes treated with intravitreal injections of ranibizumab for diabetic macular oedema.

AIMS: To describe baseline characteristics and visual outcome for eyes treated with ranibizumab for diabetic macular oedema (DMO) from a multicentre database. METHODS: Structured clinical data were anonymised and extracted from an electronic medical record from 19 participating UK centres: age at first injection, ETDRS visual acuity (VA), number of injections, ETDRS diabetic retinopathy (DR) and maculopathy grade at baseline and visits. The main outcomes were change in mean VA from baseline, number of injections and clinic visits and characteristics affecting VA change and DR grade. RESULTS: Data from 12 989 clinic visits was collated from baseline and follow-up for 3103 eyes. Mean age at first treatment was 66 years. Mean VA (letters) for eyes followed at least 2 years was 51.1 (SD=19.3) at baseline, 54.2 (SD: 18.6) and 52.5 (SD: 19.4) at 1 and 2 years, respectively. Mean visual gain was five letters. The proportion of eyes with VA of 72 letters or better was 25% (baseline) and 33% (1 year) for treatment naïve eyes. Eyes followed for at least 6 months received a mean of 3.3 injections over a mean of 6.9 outpatient visits in 1 year. CONCLUSIONS: In a large cohort of eyes with DMO treated with ranibizumab injections in the UK, 33% of patients achieved better than or equal to 6/12 in the treated eye at 12 months compared with 25% at baseline. The mean visual gain was five letters. Eyes with excellent VA at baseline maintain good vision at 18 months.

Ocular features in neurosarcoidosis.

BACKGROUND/AIMS: To determine the type of ocular involvement in patients with neurosarcoidosis, and evaluate whether the type of eye involvement may help in the diagnosis of neurosarcoidosis. METHODS: Retrospective, case history study. We reviewed the medical records of 46 patients who attended the sarcoidosis clinics at the Royal Brompton and Moorfields Eye Hospital over a 4-year period with a diagnosis of definite and probable neurosarcoidosis supported by laboratory investigations and exclusion of other causes for the neurological symptoms. RESULTS: Cranial nerve involvement was the most common neurological manifestation in this series. Among the 27 patients with cranial neuropathy, lower motor neurone facial palsy was the most frequently seen in 19 patients (70.4%). Diplopia was seen in four patients (14.9%). In three patients, this was because of common oculomotor nerve paresis. Uveitis was the most common intraocular manifestation in patients with neurosarcoidosis. The majority of these patients (9, 64.3%) suffered from anterior uveitis, but in 35.7% of them the inflammatory process involved the posterior segment. CONCLUSIONS: We found a higher incidence of ocular manifestations, including intraocular inflammation in neurosarcoidosis compared to that in systemic sarcoidosis elsewhere. The most common ocular complication seen in our series was anterior uveitis; however there were no associated clinical features of the uveitis in these series that could contribute to the differential diagnosis between neurosarcoidosis and other autoimmune disorders with neuro-ophthalmic features such as multiple sclerosis. Patients with neurological symptoms and associated intraocular inflammation should have a routine work-up for sarcoidosis. Investigations should include MRI scan of the brain and orbits and lumbar puncture in selected cases. Tissue biopsy should be attempted when clinically accessible lesions are available i.e., conjunctiva or lacrimal gland.

Protocol for the use of polymerase chain reaction in the detection of intraocular large B-cell lymphoma in ocular samples.

To determine the usefulness of polymerase chain reaction (PCR) analyses in the diagnosis of lymphoid infiltrate cells in ocular samples, PCR was performed using oligonucleotide primers specific for immunoglobulin heavy chain rearrangement at framework 2, framework 3, and t(14;18) translocation of the bcl-2 gene. These were used to successfully generate amplicons of 220 to 230 bp, 110 to 120 bp, and 175 to 200 bp, respectively. After PCR amplification, primers directed against the t(14;18) detected 10 pg of B-cell lymphoma DNA. PCR against Fr2 and Fr3 IgH rearrangement detected 10 fg and 10 pg in the seminested PCR, respectively. Conventional pathological methods were highly accurate at establishing the correct final diagnosis in formalin-fixed, paraffin-embedded samples but were much less sensitive and predictive in cytological specimens of intraocular fluid. A combination of the three PCR reactions was an equally successful diagnostic approach on paraffin-embedded samples, whereas single PCR reactions did not significantly improve diagnosis over histopathological diagnostic techniques. Thus, a combination of PCR reactions is useful in the detection of B-cell monoclonality, aids the differentiation between lymphomatous and inflammatory infiltrates, and is more powerful as a diagnostic method than single PCR or conventional cytopathology for lymphoid infiltrates in ocular fluid aspirates.

Visual loss in sarcoid-related uveitis.

PURPOSE: To assess the visual acuity outcome after treatment, in patients with differing types of uveitis associated with sarcoidosis, and to determine the types of sight-threatening complications. METHODS: This was an retrospective, non-comparative, interventional study of patients who had uveitis with a confirmed diagnosis of sarcoidosis and a minimum follow-up duration of 6 months from presentation. The worst affected eye at presentation was selected for the study. Complications causing impaired vision were documented, changes in visual acuity after completion of treatment were measured, and the risk of 'poor outcome' (visual acuity 6/12 and less) was compared in the various types of uveitis, using 'exact' multiple logistic regression to control confounding by other prognostic factors. RESULTS: Seventy-five patients were studied. The spectrum of ocular inflammation in sarcoidosis is wide. Presentation may be acute and non-granulomatous or chronic and granulomatous with posterior segment involvement being varied. Poor visual outcome was significantly more frequent in multifocal choroiditis (5/7, 71.4%), and in panuveitis without multifocal choroiditis (13/28, 46.4%), compared to only 3/24 (12.5%) patients with anterior uveitis. The excess risks remained significant after adjustment for confounding effects of other prognostic factors including age, sex and manifest systemic sarcoidosis. Causes of visual loss were cataract, glaucoma, macular oedema, vitreous haemorrhage and retinal detachment. CONCLUSION: Multifocal choroiditis is a less common manifestation of uveitis associated with sarcoidosis but appears to be associated with a worse visual prognosis despite immunosuppressive therapy.

Vitreous aspiration needle tap in the diagnosis of intraocular inflammation.

PURPOSE: To determine the safety of vitreous aspiration needle tap as a clinical procedure and its usefulness in helping to distinguish between infective, inflammatory, and malignant causes of uveitis. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Data were collected for 53 patients who had undergone vitreous aspiration needle tap as an outpatient in the clinic. METHODS: These patients underwent vitreous aspiration needle tap using a needle and syringe for the following indications: (1) when masquerade syndrome or infective retinitis was the primary diagnosis; and (2) to diagnose or exclude infective or malignant entities in patients not responding to treatment. The result of the analysis of the biopsy specimen and any complications that arose from the procedure were determined. RESULTS: In this series, vitreous aspiration needle tap generated an adequate sample for the relevant investigations in 92% of cases. The initial diagnosis of intraocular malignancy or infection was confirmed in 40% of patients. The remaining patients were treated with immunosuppressives for the ocular inflammation and showed clinical improvement over the follow-up period. Multiple procedures were required in two patients to make the diagnosis of B-cell intraocular lymphoma and in two patients with acute retinal necrosis who were treated for the presenting clinical features. CONCLUSIONS: Vitreous aspiration needle tap would seem to be a safe clinical procedure, which has a high success rate in differentiating between infectious, inflammatory, and malignant causes of uveitis. It is a quick procedure that can be carried out at the first outpatient visit.

Pseudo-hypopyon as the presenting feature in B-cell and T-cell intraocular lymphoma.

The clinicopathologic correlation of two patients with primary intraocular lymphoma is described, both of whom had a rare and unusual presentation of hypopyon uveitis. Sampling of aqueous fluid proved the cytopathologic diagnosis of B-cell lymphoma in the first patient. In the second patient an iris biopsy confirmed a T-cell lymphoma. The samples were examined using haematoxylin and eosin, and immunohistochemical stains. These patients were diagnosed with primary intraocular lymphoma on initial presentation with hypopyon uveitis. Secondary glaucoma was noted in the patient with T-cell lymphoma. Both cases appeared confined to the eye and initially responded favourably to aggressive chemotherapy and radiotherapy, but later went on to develop systemic involvement. Clinicians should be aware of this dramatic mode of presentation, which is unusual for ocular lymphoma.