Aflibercept in clinical practice; visual acuity, injection numbers and adherence to treatment, for diabetic macular oedema in 21 UK hospitals over 3 years.

INTRODUCTION: Randomised controlled trials provide evidence that a treatment works. Real world evidence is required to assess if proven treatments are effective in practice. METHOD: Retrospective data collection on patients given aflibercept for diabetic macular oedema over 3 years from 21 UK hospitals: visual acuity (VA); Index of multiple deprivation score (IMD); injection numbers; protocols used, compared as a cohort and between sites. RESULTS: Complete data: 1742 patients (from 2196 eligible) at 1 year, 860 (from 1270) at 2, 305 (from 506) at 3 years. The median VA improved from 65 to 71, 70, 70 (ETDRS letters) at 1, 2 and 3 years with 6, 9 and 12 injections, respectively. Loss to follow-up: 10% 1 year, 28.8% at 3. Centres varied: baseline: mean age 61-71 years (p < 0.0001); mean IMD score 15-37 (p < 0.0001); mean VA 49-68 (p < 0.0001). Only four centres provided a loading course of five injections at monthly intervals and one 6. This did not alter VA outcome at 1 year. Higher IMD was associated with younger age (p = 0.0023) and worse VA at baseline (p < 0.0001) not total number of injections or change in VA. Lower starting VA, higher IMD and older age were associated with lower adherence (p = 0.0010). CONCLUSIONS: The data showed significant variation between treatment centres for starting age, VA and IMD which influenced adherence and chances of good VA. Once treatment was started IMD did not alter likelihood of improvement. Loading dose intensity did not alter outcome at one year.

[Acute macular neuroretinopathy]. / Akute makuläre Neuroretinopathie.

A 24-year-old female patient presented with sudden onset of paracentral visual field defects of the right eye, which were noticed 2 months before the clinical examination. The slit lamp examination of the anterior and posterior segments showed unremarkable findings but three oval, well demarcated, hyporeflective areas were noticed in the right posterior pole in infrared fundus photographs. A similar small area was found in the left posterior pole. Optical coherence tomography (Cirrus OCT) showed a structural defect of the hyperreflective bands of the outer retina. The diagnosis of acute macular neuroretinopathy was made.

Pseudoxanthoma elasticum: biopsy of clinically normal skin in the investigation of patients with angioid streaks.

BACKGROUND: Pseudoxanthoma elasticum (PXE) is a genetic disorder characterized by fragmentation and calcification of elastic fibres with resultant pathological changes in the dermis, Bruch's membrane and blood vessels. Defects in Bruch's membrane produce angioid streaks on the retina but this appearance is not pathognomonic of PXE. Biopsy of clinically normal skin or scar tissue in patients with angioid streaks may show the histological features of PXE. OBJECTIVES: To test the hypothesis that biopsy of clinically normal skin is a useful investigation in patients with angioid streaks. METHODS: This prospective study investigated 18 consecutive patients with angioid streaks. Each patient underwent a full dermatological examination and was investigated for diseases known to be associated with angioid streaks. Axillary skin biopsies were taken from 14 consenting patients. RESULTS: Typical PXE was found in 11 patients. No other diseases associated with angioid streaks were identified. Five patients had angioid streaks in the absence of systemic disease. Two patients had nondiagnostic dermatological features which were not clarified by histology. Two of the 11 patients with PXE showed histological evidence of PXE from clinically normal axillary skin. However, in both cases flexural skin elsewhere showed the typical clinical and histological features of PXE. CONCLUSIONS: This study demonstrates the association between angioid streaks and PXE. However, it does not support the hypothesis that biopsy of normal-looking skin is helpful in the investigation of adult patients with angioid streaks.

Correlation of optical coherence tomography and fundus fluorescein angiography following photodynamic therapy for choroidal neovascular membranes.

AIMS: To assess the correlation between optical coherence tomography (OCT) and leakage on fundus fluorescein angiography (FFA) following photodynamic therapy (PDT) with verteporfin for choroidal neovascularisation (CNV). METHODS: Retrospective comparative observational case series of patients who were treated with PDT for CNV from one centre. All patients had 3 monthly FFA and OCT following initial PDT to assess if further treatment was required. A pair of FFA and OCT images from the same visit at a random follow up date were taken from each patient's series and assessed separately by different observers. The presence of pigment epithelial detachment, subretinal fluid, vitreomacular traction, intraretinal fluid, absence of foveal depression, and the retinal thickness on OCT were correlated with presence of leaks on FFA. RESULTS: A total of 121 eyes of 121 patients were included. The presence of subretinal fluid, gross cystoid macular oedema, sponge-like retinal thickening and retinal thickness of more than 350 mum on OCT correlated well with leak on FFA (p value <0.01). The likelihood ratios were 3.0, 5.7, 2.7, and 3.6, respectively. The presence of a solitary foveal cyst did not correlate well with leaks on FFA. CONCLUSIONS: The presence of subretinal fluid, intraretinal fluid in the form of gross cystoid macular oedema, or sponge-like retinal thickening, or a retinal thickness more than 350 mum correlates with leaks on FFA and so suggests the need for repeat PDT.

Correlation of optical coherence tomography, with or without additional colour fundus photography, with stereo fundus fluorescein angiography in diagnosing choroidal neovascular membranes.

AIMS: To assess the diagnostic accuracy of optical coherence tomography (OCT), with/without colour fundus photographs, in predicting fundus fluorescein angiography (FFA) findings in patients suspected of having choroidal neovascularisation (CNV). METHODS: A consecutive series of patients suspected of having CNV underwent OCT and stereo FFA images, which were assigned a diagnosis by two masked observers, one examining OCT alone and then OCT plus stereo colour photographs, and one examining FFA alone. The main outcome measures were the diagnostic accuracy of OCT (with/without colour photos) in predicting the presence of CNV and secondly the characteristics of the CNV compared to the FFA findings. RESULTS: 131 eyes of 118 patients were analysed. The sensitivity and specificity of OCT for detecting new potentially treatable CNV lesions compared to FFA was 96.4%, and 66.0%, respectively. For OCT with stereo images the sensitivity was 94.0% and specificity 89.4%. For detecting CNV with a classic component the sensitivity and specificity of OCT alone was 78.6% and 82.7%. With stereo colour images the sensitivity was 82.1% and specificity 89.3%. CONCLUSION: OCT is good at detecting the presence of CNV in patients suspected of having new CNV. However, it is less accurate at identifying the exact components of CNV. OCT cannot at present replace FFA in accurately diagnosing CNV components. However, this imaging method may have a role as a screening tool to help prioritise FFA requests.

Verteporfin photodynamic therapy of choroidal neovascularization in angioid streaks: one-year results of a prospective case series.

PURPOSE: To report the 12-month results on the use of verteporfin photodynamic therapy (PDT) in the treatment of choroidal neovascularization (CNV) secondary to angioid streaks. STUDY DESIGN: Five-center prospective case series. METHODS: Patients with CNV secondary to angioid streaks who were treated with PDT were recruited and followed up at 3-month intervals for 12 months, with the addition of visits at 1.5 and 4.5 months if deemed appropriate by the investigator. Best-corrected visual acuity (BCVA) was measured at each visit after full refraction or with their current distance spectacles using Early Treatment Diabetic Retinopathy Study logarithm of the minimum angle of resolution charts. Stereoscopic fundus fluorescein angiography was used to determine baseline lesion characteristics and location. RESULTS: Twenty-two patients were recruited (23 eyes, 16 with subfoveal CNV and 7 with juxtafoveal; all classic no occult). Seventeen patients (77%) had angioid streaks secondary to pseudoxanthoma elasticum. In the subfoveal group, median BCVA at baseline was 49 letters (approximate Snellen equivalent, 20/100) and was 46 at 12 months (approximate Snellen equivalent, 20/125). Twelve of 16 eyes (75%) lost fewer than 8 letters, whereas 14 of 16 eyes (88%) lost fewer than 15 letters. The mean CNV greatest linear dimension (GLD) was 2520 microm at baseline. At 12 months, 7 of 16 eyes with subfoveal CNV at baseline were leaking (GLD = 3220 microm; P = 0.62). The mean number of treatments in the first 12 months was 2.9. In the juxtafoveal group, the median BCVA at baseline was 66 letters (approximate Snellen equivalent, 20/50) and was 51 letters at 12 months (approximate Snellen equivalent, 20/100). Two of 7 eyes (29%) gained 8 or more letters at the 12-month examination, whereas 4 of 7 eyes (57%) lost more than 15 letters. The mean CNV GLD at baseline was 1890 microm. At 12 months, 1 of 7 eyes with juxtafoveal CNV at baseline was leaking. Choroidal neovascularization progressed from juxtafoveal to subfoveal location during the follow-up period in 4 of 7 eyes. The mean number of treatments in the first 12 months was 3.4. No side effects were noted in either patient group. CONCLUSIONS: This small series suggests that treatment of CNV secondary to angioid streaks with verteporfin PDT seems to limit visual loss in most patients through the first 12 months of follow-up, particularly in those with subfoveal lesions at baseline.

The incidence and outcome of photodynamic therapy for macular degeneration in the Northern region of the UK.

PURPOSE: To assess the patients who have had photodynamic therapy (PDT) in the Northern region of the UK, in relation to the eligibility criteria found to benefit in the TAP study (treatment of age-related macular degeneration with photodynamic therapy study), so as to make an estimate of the number of patients who might benefit from this treatment and to present the outcome of the treatment so far. METHOD: The records and fluorescein angiograms (FFAs) of all patients who had had PDT in the Northern region between 2001 and 2002 were reviewed for compliance with the TAP criteria of >50% classic choroidal neovascularization and >34 letters on the 2 m logMAR Early Treatment Diabetic Retinopathy Study chart. NHS funding has been available in the Northern Region since January 2001 for 'second eye' involvement. A review of all the angiograms performed for exudative macular degeneration in 1 year was also performed. The visual outcome of those patients 1 year from baseline was measured. RESULTS: A total of 82 'second eye' patients were treated between January 2001 and December 2002. This gives an incidence of 65 per 3 million and so about 1300 in the whole of the UK (population 60 million). In all, 238 FFAs were performed on exudative macular degeneration, with 21% being found eligible for PDT. As of February 2003, 54 TAP criteria, macular degeneration patients were 1 year from initial treatment. Of these, 12 had incomplete follow-up and 13 patients had lost more than 15 letters. The responder rate defined as losing <15 letters was 42-13/42=69%. Seven of those who did not make 1-year follow-up had lost more than 15 letters when last seen, giving a responder rate of 54-20/54=63%. CONCLUSION: There may not be as many patients eligible for PDT, using the TAP criteria, as previously hoped. The outcome of treatment appears similar to that found in the TAP study.

Delayed dislocation of foldable plate-haptic silicone lenses after Nd:YAG laser anterior capsulotomy.

PURPOSE: To report two eyes (two patients) that had plate haptic silicone intraocular lenses that dislocated 4 weeks after Nd:YAG laser anterior capsulotomy to relieve capsular contraction. METHODS: Case reports. The clinical records of two patients were reviewed. RESULTS: After uncomplicated phacoemulsification with implantation of plate haptic silicone lenses in the capsular bag, two eyes of two patients developed visually notable early contraction of the capsulorhexis. Three radial-relieving incisions approximately 1 mm long were made with a Nd:YAG laser in each eye to enlarge the capsulotomy. Although vision improved, both patients experienced sudden further reduction of vision after approximately 4 weeks. Upon examination of both patients, we noted an extension of an anterior radial capsulotomy incision peripherally, and the intraocular lenses had dislocated from the capsular bag into the ciliary sulcus. CONCLUSIONS: Tears may extend after radial-relieving incisions have been used to enlarge a contracted anterior capsulotomy, possibly because of continued capsular fibrosis. This may allow extrusion of a foldable intraocular lens from the capsular bag.

The contribution of macular changes to visual loss in benign intracranial hypertension.

PURPOSE: To describe the significance of macular changes to visual outcome in benign intracranial hypertension (BIH). METHOD: The clinical and photographic records of 24 patients with BIH who required optic nerve sheath fenestration were analysed. RESULTS: Macular changes were found in 21 of 48 (44%) eyes. These were: choroidal folds 9; circumferential lines (Paton's lines) 4; nerve fibre layer haemorrhage 3; macular stars 5; macular oedema 6; retinal pigment epithelial changes 4; subretinal haemorrhage leading to a macular scar 1. Significant visual loss attributable to the macular changes was found in 5 eyes in the short term and 3 in the long term. The 2 eyes that improved had macular stars. Of the 3 eyes that did not improve, 2 eyes had retinal pigment epithelial changes and 1 a large subretinal haemorrhage that led to a macular scar. These 3 cases had long-standing BIH. CONCLUSIONS: The majority of macular changes resolve and do not add to visual loss from optic nerve damage. Patients with marked macular oedema are at most risk of permanent visual loss and should be considered for early treatment such as optic nerve sheath fenestration.

Cavernous-dural fistula with secondary angle-closure glaucoma.

PURPOSE: To report a rare case of angle-closure glaucoma, secondary to the rapid development of a choroidal effusion, in a patient with a long-standing cavernous-dural shunt. METHODS: Case report. Investigations included computed tomographic scan, magnetic resonance imaging, and carotid angiography. RESULTS: The development of the choroidal effusion occurred because of partial thrombosis of the ipsilateral superior ophthalmic vein and cavernous sinus. Drainage of the choroidal effusion resolved the angle-closure glaucoma. CONCLUSIONS: The combination of worsening signs and evidence of thrombosis indicates impending resolution of a cavernous-dural shunt. However, if a choroidal effusion causes angle-closure glaucoma, prompt surgical drainage should be considered to prevent permanent peripheral anterior synechiae formation, with the expectation that the effusion will not recur.