Christine A. Kiire

High prevalence of sleep disordered breathing in patients with diabetic macular edema.

Background: Diabetic retinopathy is more common and severe in patients with sleep disordered breathing (SDB). This study aimed to establish whether this is also true for patients with diabetic clinically significant macular edema (CSME). It is hypothesized that SDB, through intermittent hypoxia and blood pressure oscillations, might provoke worsening of CSME. Methods: Patients with CSME had a home sleep study (ApneaLink; ResMed) to identify SDB. These results were compared with relevant control populations. Macular thickness was measured using optical coherence tomography, and retinal photographs were graded to assess the severity of retinopathy. Results: Eighty of 195 patients (40 men) consented, with average age of 64.7 (11.7) years, neck circumference of 40.4 (5.4) cm, body mass index of 30.2 (6.2) kg/m2, glycosylated hemoglobin (HbA1c) 7.8% (1.4%) [62 (8.0) mmol/mol], and Epworth sleepiness scale of 7.4 (4.8). Overall, 54% had an oxygen desaturation index ≥10, and 31% had an apnea-hypopnea index ≥15. This SDB prevalence is probably higher than would be expected from the available matched control data. Those with SDB were not sleepier, but they were older and more obese. No significant relationship was identified between the degree of macular thickness and the severity of SDB. Conclusion: Individuals with CSME have a high prevalence of SDB. Sleep disordered breathing may contribute to the pathophysiology of CSME, but the mechanism remains unclear. Given the high prevalence, retinal specialists should perhaps consider a diagnosis of SDB in patients with CSME.

Ocular surface squamous neoplasia.

Ocular surface squamous neoplasia (OSSN) is an umbrella term that encompasses dysplasia, carcinoma in situ, intraepithelial neoplasia, and squamous cell carcinoma (SCC) of the cornea and/or conjunctiva. The majority of advances in our understanding of how best to diagnose and treat this condition have taken place in the last 20 years. This has coincided with a significant change in the epidemiologic pattern of the disease. Most studies of the prevalence of OSSN were concluded more than 10 years ago. The incidence has been estimated to range between <0.2 cases/million/year (UK, 1996) and 35 cases/million/year (Uganda, 1992). It is on the increase in Africa and is seen in Asia too. In 2003, the balance of epidemiologic evidence suggested that the highest risk of OSSN was in older white men of Caucasian origin, particularly those living closer than 30-degrees latitude from the equator. Lee and Hirst (1992) noted a preponderance of male cases of OSSN. Tunc et al analyzed 60 cases of OSSN and found that the mean age of their patients was 64, and that 70% of patients were male. This may well remain the case among whites in the West. In Africa, however, OSSN has been behaving differently. Younger people have been affected with more aggressive tumors at a younger age. Patients with xeroderma pigmentosum and human immunodeficiency virus may also develop OSSN at a younger age.

Visual improvement following continuous positive airway pressure therapy in diabetic subjects with clinically significant macular oedema and obstructive sleep apnoea: proof of principle study.

Background: Diabetic retinopathy and diabetic macular oedema are more prevalent in patients with coexistent obstructive sleep apnoea (OSA). Objectives: We assessed if treatment of OSA with continuous positive airway pressure (CPAP) might improve visual acuity (VA). Methods: A total of 35 patients with clinically significant macular oedema (CSMO) and OSA [oxygen desaturation index (ODI) ≥10 or apnoea-hypopnoea index (AHI) ≥15] were identified and agreed to be studied. VA (expressed as the logarithm of the minimum angle of resolution, logMAR), macular thickness, fundal photographs, glycosylated haemoglobin (HbA1c) and rhodopsin mRNA were measured twice at baseline and at 3 and 6 months post-CPAP. Fluorescein angiography and the Epworth Sleepiness Scale (ESS) were obtained once at baseline and at 6 months. Results: Three patients withdrew before the first trial visit. Thus, a total of 32 patients (17 males) entered the study, and 4 subsequently withdrew; thus 28 completed 6 months of follow-up. Baseline characteristics of the subjects were as follows [mean (SD or inter-quartile range)]: age 66.2 (7.1) years, body mass index 31.7 (6.3), HbA1c 7.4% (1.44) [57.1 (15.7) mmol/mol], AHI 16.5 (11–25), ODI 16.0 (12–25), ESS 6.5 (4.0–12.0) and duration of diabetes 9.5 years (5.0–16.5). Participants were divided into 13 high and 15 low CPAP compliers (≥ and <2.5 h/night over the 6 months, respectively). At 6 months, the adjusted treatment effect on VA of high compliance versus low compliance was 0.11 (95% confidence interval 0.21 to –0.002; p = 0.047), equivalent to a one-line improvement on the logMAR chart. There was no significant improvement in macular oedema or fundal photographs. Conclusions: This hypothesis-generating, uncontrolled study suggests that ≥2.5 h/night CPAP usage over 6 months in individuals with CSMO and OSA may be associated with improvement in VA. This provides justification for a randomised controlled trial of CPAP therapy in such patients.

Medical management for the prevention and treatment of diabetic macular edema

Recent clinical trials have changed the management paradigm for diabetic macular edema (DME). There is an urgent need to identify the most effective ways of preventing retinopathy or intervening at an early, asymptomatic stage in order to preserve vision. The rise in the incidence of diabetes is a serious public health concern. Grading and screening programmes help to identify sight threatening diabetic retinopathy in the community early and facilitate timely referral to an ophthalmologist. Systemic therapies for DME target the key modifiable risk factors: metabolic and blood pressure control. There may also be a role for modification of the renin-angiotensin system and for lipid lowering agents. Improved glycemic and blood pressure control remain the most effective ways of reducing morbidity from DME. Fenofibrate also has beneficial effects, but the mechanism for this remains unclear. Multiple new treatments are in the pipeline, and these are expected to change our approach to DME for the first time in 30 years.

Managing antiplatelet and anticoagulant drugs in patients undergoing elective ophthalmic surgery

The management of antiplatelet and anticoagulant treatment can be challenging for the ophthalmic surgeon with the risk of impaired surgical view or potentially sight-threatening haemorrhage. With the advent of newer medications and the expanding usage of these drugs, there is a need for up-to-date guidance on the subject. This paper describes the current use of modern antiplatelet and anticoagulant drugs in the UK, and reviews the evidence of such treatments in the context of ophthalmic surgery. A multidisciplinary approach has been used to develop a guideline for the management of antiplatelet and anticoagulation treatment in elective ophthalmic surgery. Specifically, guidance is provided on when and how to stop antiplatelet and anticoagulant treatment and, importantly, when to seek specialist medical advice.

Intravitreal pegaptanib for the treatment of ischemic diabetic macular edema.

Purpose Pegaptanib has been shown to be effective in treating diabetic macular edema (DME). In the original Phase II/III trial, however, patients with macular ischemia were excluded. In this study, we treated patients with ischemic DME. Methods Macular ischemia was defined as a 30% increase in the area of the foveal avascular zone (FAZ) at 45 seconds on fundus fluorescein angiography. In addition, the participants had diffuse foveal-involving DME with a central subfield thickness (CST) of >300 μm on spectral-domain optical coherence tomography. Five intravitreal pegaptanib injections were given 6 weeks apart. The final study visit was 6 weeks after the fifth injection. The primary outcome was change in the size of FAZ. Secondary outcomes were change in best-corrected visual acuity (BCVA) and the change in CST. Results Thirty participants were enrolled. Three were unable to complete the full course of treatment. Their outcomes were carried forward for the first part of this analysis. There was no statistically significant change in the mean size of the FAZ from baseline to the final visit. Subclassifying participants as those with minimal/moderate ischemia (16 participants, FAZ area <1,000 pixels) and those with more severe ischemia (14 participants, FAZ area >1,000 pixels) also showed no statistically significant change in the mean area of the FAZ. On average, BCVA increased and CST decreased from baseline to the final visit, but these changes were not statistically significant. Using per protocol analysis on those participants who completed the full course of treatment, the mean BCVA increased from 49.2 to 53.9 letters (P=0.046). Conclusion In this study, intravitreal injection of pegaptanib did not significantly alter the size of the FAZ in participants with varying degrees of ischemic DME. There was, however, a significant improvement in mean BCVA in those who completed the treatment course.

Peripheral ulcerative keratitis after cataract surgery in a patient with ocular cicatricial pemphigoid.

Purpose: To describe a case of peripheral ulcerative keratitis (PUK) that developed in the immediate postoperative period after uncomplicated cataract surgery in a patient with ocular cicatricial pemphigoid. Methods: Single interventional case report. An elderly white woman with stable ocular cicatricial pemphigoid underwent an uncomplicated clear corneal phacoemulsification procedure in the left eye. In the immediate postoperative period, PUK developed adjacent to the corneal wound in the left eye. Results: The PUK was successfully treated with a bandage contact lens to the left eye, optimizing the ocular surface with punctal plugs and topical and systemic steroid therapy. After a 7-week course of tapering topical and systemic steroids, the PUK completely resolved. There was no further flare-up over a 12-month period. Conclusions: PUK can develop after clear corneal cataract surgery in patients with stable ocular cicatricial pemphigoid. Perioperative immunosuppression should be considered to minimize the chance of PUK developing in such cases.

A novel use of fibrin glue in the treatment of a partial thickness corneal laceration

We describe a novel technique on the use of fibrin glue to seal a longstanding partial thickness corneal laceration. A 67-year-old lady was referred to the corneal service with an asymptomatic, partial thickness corneal laceration in the right eye (RE) that had failed to heal spontaneously over a 12-month period. She had no recollection of any history of trauma to that eye, but the laceration appeared clean-cut with well-defined edges, indicating that a sharp object may have caused it. On examination, the best corrected visual acuities were 6/12 RE and 6/6 in her pseudophakic LE. Slit-lamp biomicroscopy of her RE showed a partial thickness corneal laceration 6 mm in length. It started close to the inferotemporal limbus and extended towards the central cornea without passing through the visual axis (figure 1). On high magnification, there were classic epithelial pearls on the surface of …

Managing antiplatelet and anticoagulant drugs in patients undergoing elective ophthalmic surgery. Authors' response.

We thank Grzybowski et al for their comments on our paper. The main contention of the authors is that patients undergoing cataract surgery with antiplatelet (Ap) and/or anticoagulant (Ac) medications should continue to receive these drugs based on evidence in the medical literature. In our paper, we clearly acknowledge that the predominant technique for lens extraction is phacoemulsification, and that the risk of complications related to bleeding is rare. In one of the papers referenced by Grzybowski et al, a small, but not insignificant, risk of intraoperative haemorrhage in patients undergoing cataract surgery is mentioned, with no reported effect on visual outcome. The meta-analysis did not, however, specifically review patients with a target international normalised ratio (INR) of over 3 or those on dual therapy (ie, warfarin and aspirin). Benzimra et al conducted a large retrospective study using electronic patient records and once again found that there was no increased risk of sight-threatening complications related to the administration of local anaesthetic or cataract surgery itself, in patients who were recorded as previously taking Ap/Ac therapy. This paper did not review whether such therapy had been discontinued or modified prior to cataract surgery which could result in under-reporting of complications. Moreover, there was no mention made of the clinical indication for Ap/Ac therapy or a target INR in patients taking warfarin which has relevance. Clearly there is a paucity of evidence on which to base practice for every possible situation, particularly for patients on novel therapies such as Apixiban and Dabigatran. We have outlined a risk stratification strategy to take into consideration an assortment of clinical scenarios. In our opinion, adopting a ‘one size fits all approach’ is inadvisable for patients on Ap/Ac therapy and we would recommend an individualised approach. For example, a patient with only one eye and a metallic heart valve on dual Ap/Ac therapy with a target INR of 3.5 will require a more judicious approach than a patient on single agent therapy for primary prevention. In conclusion, we would agree that continuation of antiplatelet and/or anticoagulant medications in the vast majority of patients undergoing cataract surgery is the correct approach. We would also advise that the clinician has a rudimentary knowledge of such therapy and is, therefore, able to pre-empt and manage situations where the potential risks to life or vision is increased. Rajarshi Mukherjee, Christine A Kiire, Neil Ruparelia, David Keeling, Bernard Prendergast, Jonathan H Norris