Action on diabetic macular oedema: achieving optimal patient management in treating visual impairment due to diabetic eye disease.

This paper identifies best practice recommendations for managing diabetes and sight-threatening diabetic eye disease. The authors provide an update for ophthalmologists and allied healthcare professionals on key aspects of diabetes management, supported by a review of the pertinent literature, and recommend practice principles for optimal patient management in treating visual impairment due to diabetic eye disease. In people with diabetes, early optimal glycaemic control reduces the long-term risk of both microvascular and macrovascular complications. The authors propose more can and should be done to maximise metabolic control, promote appropriate behavioural modifications and encourage timely treatment intensification when indicated to ameliorate diabetes-related complications. All people with diabetes should be screened for sight-threatening diabetic retinopathy promptly and regularly. It is shown that attitudes towards treatment adherence in diabetic macular oedema appear to mirror patients' views and health behaviours towards the management of their own diabetes. Awareness of diabetic macular oedema remains low among people with diabetes, who need access to education early in their disease about how to manage their diabetes to delay progression and possibly avoid eye-related complications. Ophthalmologists and allied healthcare professionals play a vital role in multidisciplinary diabetes management and establishment of dedicated diabetic macular oedema clinics is proposed. A broader understanding of the role of the diabetes specialist nurse may strengthen the case for comprehensive integrated care in ophthalmic practice. The recommendations are based on round table presentations and discussions held in London, UK, September 2016.

South Asian diabetic macular oedema treated with ranibizumab (ADMOR)-real-life experience.

PURPOSE Diabetic macular oedema (DMO) is a leading cause for visual impairment in the working age population in the UK. Ranibizumab has been shown to be effective in treatment of DMO in studies based on mainly Caucasian populations. This study reports the 12-month outcome in a cohort of South Asian subjects with DMO treated with ranibizumab.MethodsDMO in 51 eyes of 41 South Asian patients was treated with ranibizumab 0.5 mg according to the modified DRCRnet protocol I. Visual acuity (VA) and central macular thickness (CMT) were recorded at baseline, 3, 6, and 12 months. Results were compared for eyes with different baseline visual acuities and different baseline macular thicknesses.RESULTS Over the 12-month period, the mean ETDRS VA increased from 55.3±13.4 letters to 63.8±15.2 letters for all eyes. At 12 months, 70.6% eyes gained 5 or more letters acuity and 17.6% eyes gained 15 letters or more. During the same period, the mean CMT decreased from 532±129 to 318±136 µm. Eyes that had received previous laser treatments had a mean letter gain of 9.2 letters, compared with 8.5 for all eyes at 12 months.CONCLUSIONS Ranibizumab 0.5 mg is safe and effective at reversing vision loss due to DMO in patients of South Asian origin at 12 months. Ranibizumab treatment appears to be effective in patients with longstanding DMO who received prior laser treatments. Further studies are needed to define the long-term outcome in patients of different ethnicity and DMO.

Defining response to anti-VEGF therapies in neovascular AMD.

The introduction of anti-vascular endothelial growth factor (anti-VEGF) has made significant impact on the reduction of the visual loss due to neovascular age-related macular degeneration (n-AMD). There are significant inter-individual differences in response to an anti-VEGF agent, made more complex by the availability of multiple anti-VEGF agents with different molecular configurations. The response to anti-VEGF therapy have been found to be dependent on a variety of factors including patient's age, lesion characteristics, lesion duration, baseline visual acuity (VA) and the presence of particular genotype risk alleles. Furthermore, a proportion of eyes with n-AMD show a decline in acuity or morphology, despite therapy or require very frequent re-treatment. There is currently no consensus as to how to classify optimal response, or lack of it, with these therapies. There is, in particular, confusion over terms such as 'responder status' after treatment for n-AMD, 'tachyphylaxis' and 'recalcitrant' n-AMD. This document aims to provide a consensus on definition/categorisation of the response of n-AMD to anti-VEGF therapies and on the time points at which response to treatment should be determined. Primary response is best determined at 1 month following the last initiation dose, while maintained treatment (secondary) response is determined any time after the 4th visit. In a particular eye, secondary responses do not mirror and cannot be predicted from that in the primary phase. Morphological and functional responses to anti-VEGF treatments, do not necessarily correlate, and may be dissociated in an individual eye. Furthermore, there is a ceiling effect that can negate the currently used functional metrics such as >5 letters improvement when the baseline VA is good (ETDRS>70 letters). It is therefore important to use a combination of both the parameters in determining the response.The following are proposed definitions: optimal (good) response is defined as when there is resolution of fluid (intraretinal fluid; IRF, subretinal fluid; SRF and retinal thickening), and/or improvement of >5 letters, subject to the ceiling effect of good starting VA. Poor response is defined as <25% reduction from the baseline in the central retinal thickness (CRT), with persistent or new IRF, SRF or minimal or change in VA (that is, change in VA of 0+4 letters). Non-response is defined as an increase in fluid (IRF, SRF and CRT), or increasing haemorrhage compared with the baseline and/or loss of >5 letters compared with the baseline or best corrected vision subsequently. Poor or non-response to anti-VEGF may be due to clinical factors including suboptimal dosing than that required by a particular patient, increased dosing intervals, treatment initiation when disease is already at an advanced or chronic stage), cellular mechanisms, lesion type, genetic variation and potential tachyphylaxis); non-clinical factors including poor access to clinics or delayed appointments may also result in poor treatment outcomes. In eyes classified as good responders, treatment should be continued with the same agent when disease activity is present or reactivation occurs following temporary dose holding. In eyes that show partial response, treatment may be continued, although re-evaluation with further imaging may be required to exclude confounding factors. Where there is persistent, unchanging accumulated fluid following three consecutive injections at monthly intervals, treatment may be withheld temporarily, but recommenced with the same or alternative anti-VEGF if the fluid subsequently increases (lesion considered active). Poor or non-response to anti-VEGF treatments requires re-evaluation of diagnosis and if necessary switch to alternative therapies including other anti-VEGF agents and/or with photodynamic therapy (PDT). Idiopathic polypoidal choroidopathy may require treatment with PDT monotherapy or combination with anti-VEGF. A committee comprised of retinal specialists with experience of managing patients with n-AMD similar to that which developed the Royal College of Ophthalmologists Guidelines to Ranibizumab was assembled. Individual aspects of the guidelines were proposed by the committee lead (WMA) based on relevant reference to published evidence base following a search of Medline and circulated to all committee members for discussion before approval or modification. Each draft was modified according to feedback from committee members until unanimous approval was obtained in the final draft. A system for categorising the range of responsiveness of n-AMD lesions to anti-VEGF therapy is proposed. The proposal is based primarily on morphological criteria but functional criteria have been included. Recommendations have been made on when to consider discontinuation of therapy either because of success or futility. These guidelines should help clinical decision-making and may prevent over and/or undertreatment with anti-VEGF therapy.

Effects of conventional argon panretinal laser photocoagulation on retinal nerve fibre layer and driving visual fields in diabetic retinopathy.

AIMS: To determine the effects of argon green panretinal laser photocoagulation on retinal nerve fibre layer thickness, threshold visual fields, and Estermann full-binocular visual fields over time in diabetic retinopathy. METHOD: Prospective, pilot clinical study. Time-domain optical coherence tomography (TD-OCT) of the optic nerve head and 24-2 SITA-Fast Humphrey/Estermann visual fields (HVF, EVFs) recorded at baseline, 10 weeks, and 6 months post laser. Quantitative field analysis of central 10 degrees, 24 degrees, and binocular visual fields. RESULTS: A total of 10 eye samples were subjected to uncomplicated multiple-session 100 ms panretinal laser using 2000 burns, 300-microm spot, and mean power of 136 mW (SD+/-39.3). TD-OCT detected and quantified an increase in mean retinal nerve fibre layer thickness at 10 weeks (+8 microm; P<0.05) and progressive thinning at 6 months (-4 microm; P<0.05) compared with baseline. Mean threshold sensitivities, and 10 degrees and 24 degrees HVF improved at both time points in the majority (9 of 10 and 8 of 10) of patients. EVFs showed no significant change with treatment. CONCLUSIONS: This pilot study shows that conventional argon laser panretinal photocoagulation may increase the retinal nerve fibre layer thickness in the short term, presumably related to laser-induced axonal injury, with progressive thinning of nerve fibre layer over the long term. The 10 degrees and 24 degrees visual fields improved significantly after laser with no adverse effects on the UK standard driving fields.

Can intravitreal tissue plasminogen activator and SF6 gas facilitate management of macular degeneration with photodynamic therapy?

PURPOSE: To describe the safety and efficacy of intravitreal tissue plasminogen activator (tPA) and sulfur hexafluoride (SF6) gas with sequential photodynamic therapy (PDT) in the management of submacular hemorrhage (SMH) associated with macular degeneration (MD). METHODS: Consecutive case series of five patients presenting with acute SMH from neovascular MD between May 2004 and January 2006 in a UK Eye Centre. Duration of visual loss was less than 7 weeks. Treatment involved intravitreal injections of tPA, SF6 gas to achieve pneumatic displacement of SMH, and 24 hours prone posturing. Displacement of SMH was assessed by digital photography, and choroidal neovascularization (CNV) was reclassified using angiography. PDT was applied when indicated within 1 to 12 days postoperatively. RESULTS: Adequate displacement of SMH allowed visualization of CNV within 24 hours in three of five patients. One patient with large SMH of 7 weeks duration had partial displacement of SMH. Three patients were reclassified with classic CNV after tPA-SF6 injection, and successfully underwent PDT. CONCLUSIONS: Intravitreal tPA and SF6 assisted pneumatic displacement of SMH is a safe and effective intervention. This technique facilitates more accurate angiographic classification of CNV. PDT may be sequentially and rapidly applied as early as 1 day after injections. The technique may be offered to patients with neovascular MD presenting with acute SMH.

The introduction of verteporfin photodynamic therapy in the UK: PDT users group (PDTUG) surveillance programme report 1.

AIMS: To report overall patient recruitment characteristics and visual acuity (VA) outcome related to baseline lesion characteristics for patients with choroidal neovascularisation (CNV) treated with verteporfin photodynamic therapy (PDT) during its introduction into routine National Health Service practice. METHODS: Thirteen treatment centres prospectively submitted data on patients undergoing verteporfin PDT for CNV of mixed aetiology between November 1999 and May 2004 into the PDT Users Group (PDTUG) surveillance database. The primary outcome was the proportion of eyes losing <15 letters of VA at 12 and 24 months, follow-up compared with the baseline examination. RESULTS: One thousand eight hundred and ninety-four eyes of 1755 patients were analysed. Lesion characteristics at baseline were: classic no occult 1152 (67.4%), predominantly classic with occult 531 (31.1%). Recruitment rate rose steadily from 13 in the first to 188 in the final quarter. Data were available at 12 months on 1010 (53.3%) and at 24 months on 310 (16.4%) eyes. The proportion of eyes losing <15 letters was 71% (716/1010) at 12 months and 70% (217/310) at 24 months. At 12 months 91% (917/1010) of patients lost <30 letters. The mean number of PDT treatments for the cohort was 2.4 in the first 12 months. An adverse reaction or event was reported in 8.1% (364/4515) of treatments. Non-visual adverse events were infrequent. CONCLUSIONS: Efficacy and safety of verteporfin PDT in reducing vision loss in macular degeneration can be reproduced in routine clinical practice. Compared to the TAP study, the fewer treatments needed in the PDTUG cohort indicate the potential for better cost-effectiveness.

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.

Transient third nerve palsy in a young patient with intracranial arteriovenous malformation.

PURPOSE: To describe a patient with transient third nerve palsy as the possible presenting sign of intracranial arteriovenous malformation. METHOD: Case report. RESULT: A 24-year-old female presented to ophthalmic casualty with sudden onset binocular diplopia and was diagnosed to have right sided partial third nerve palsy. Within 30 hours the third nerve palsy had recovered completely. A MRI scan and subsequent carotid angiogram revealed a large, high flow, trans-cortical Spetzler-Martin grade 4 arteriovenous malformation. The feeder vessel of the AVM originated from the right middle cerebral artery. Superficial venous drainage was via the superficial middle cerebral vein to the right transverse sinus. The deep venous drainage was via thalamostriate veins into markedly dilated internal cerebral vein and vein of Galen (Great cerebral vein). Venous reflux was noted around the midbrain from the vein of Galen. CONCLUSIONS: Transient third nerve palsy may rarely occur secondary to intracranial arteriovenous malformation. Ophthalmologists should consider neuroimaging in the investigations for transient cases of III nerve palsy in young patients.

Current concepts in giant cell (temporal) arteritis.

Giant cell (temporal) arteritis continues to be a sight-threatening, systemic vasculitis with a poorly understood pathogenesis. The characteristic granulomatous inflammation of the vessel wall commonly leads to local ischemia. Recent advances in immunological investigations have characterized the cellular components of the disease process, but the etiology has so far remained unresolved. A reappraisal of the clinical features of giant cell (temporal) arteritis demonstrates the heterogeneity of the manifestations of the disease, including ischemic optic neuropathy. A range of new laboratory investigations and blood flow studies with color Doppler imaging have demonstrated promising roles, with respect to diagnosis and long-term follow-up. Prompt diagnosis and expeditious treatment require a high index of clinical suspicion, particularly for atypical cases. Corticosteroids remain the treatment of choice, other immuno-suppressive agents being used as second line steroid-sparing agents. Giant cell (temporal) arteritis leads to increased vascular and visual morbidity and, if untreated, may prove fatal. To maintain high standards of management of this enigmatic disorder, ophthalmologists need to be aware of the clinical spectrum of giant cell (temporal) arteritis and currently available diagnostic tests and treatment strategies.

Sublingual lorazepam as premedication in peribulbar anesthesia.

PURPOSE: To assess the efficacy of sublingual lorazepam in inducing amnesia when used as a premedication for peribulbar anesthesia. SETTING: Department of Ophthalmology in a large district general hospital. METHODS: Following local ethical committee approval, a prospective, randomized, placebo-controlled, double-blind study of patients having routine cataract or glaucoma surgery under local anesthetic was undertaken. Patients older than 90 years of age or who were frail, confused, or unfit for surgery were excluded, as were those who weighed less than 50 kg, swallowed the tablet, or had missing data. Sixty volunteer patients were randomly given 1 mg of lorazepam or a placebo tablet by sublingual route 1 hour preoperatively. All patients were assessed for sedation, akinesia, intraoperative analgesia, and patient response including amnesia. RESULTS: There was no significant difference between groups in sedation, analgesia, or akinesia. Overall patient response was better in the lorazepam group (P = .05). Patient-reported incidence of amnesia was significantly higher in the lorazepam than in the placebo group (P < .05). CONCLUSIONS: Sublingual lorazepam improved patient comfort by inducing amnesia, and in the low dose used in this study, did not adversely affect surgery by undue heavy sedation.

Ocular tumoral calcinosis. A clinicopathologic study.

Tumoral calcinosis is a rare systemic disorder characterized by para-articular ectopic soft-tissue calcification. This case report describes the ophthalmic features (palpebral conjunctival calcific nodules, the white limbal girdle of Vogt, disc drusen, and angioid streaks) in a 38-year-old Asian woman who had tumoral calcinosis associated with hyperphosphatemia. A morphologic study of the calcified nodules on the palpebral conjunctiva disclosed deposition of hydroxyapatite crystals in an extracellular matrix (deposit) containing alcianophilic mucopolysaccharides. Excision of the eyelid nodules was not followed by recurrence.

Herniation of lung.

Non-traumatic, acquired lung hernia of pathologic variety is rare, but can be associated with tuberculous rib osteitis.

Colour Doppler imaging in giant cell (temporal) arteritis: serial examination and comparison with non-arteritic anterior ischaemic optic neuropathy.

The ophthalmological manifestations of giant cell arteritis (GCA) present a difficult diagnostic and management problem to the ophthalmologist. The orbital circulation is frequently involved in the disease process. The effects of GCA on orbital blood flow assessed by colour Doppler imaging (CDI) were investigated in this study. Serial CDI examinations of the orbital blood vessels were performed (at presentation, 2 days, 1 week and at 1 month) on 7 patients with GCA. CDI examination at presentation was also performed on 4 patients with non-arteritic anterior ischaemic optic neuropathy (AION) for comparison. Blood flow could not be detected in up to three arteries in the affected (ipsilateral) orbit of 6 GCA patients at presentation. Five of these patients were also found to have undetectable blood flow in the posterior ciliary arteries of the contralateral orbit. Serial CDI examination revealed blood flow alterations in arteritic patients despite treatment. Return of blood flow to normal was slow, and related to the clinical features. By contrast, only 1 of the patients with non-arteritic AION showed undetectable blood flow in a posterior ciliary artery. GCA leads to widespread and prolonged alterations in orbital blood flow. CDI allows the detection and monitoring of such alterations in orbital blood flow, which correlate with the clinical features of GCA. Serial CDI examinations in GCA may be used to aid management decisions.

Facial swelling in giant cell (temporal) arteritis.

Giant cell (temporal) arteritis is a systemic vasculitis of the elderly. Facial swelling is a rare manifestation of the arteritic process. Delay in recognition of the condition can result in profound loss of vision. This report describes a biopsy-proven arteritic patient who developed anterior ischaemic optic neuropathy (AION) following facial swelling. Both arteritic AION and facial swelling responded to high-dose steroid treatment. Facial swelling in giant cell (temporal) arteritis could be an indicator of risk of AION. Intravenous steroid treatment can lead to salvation of useful vision.