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Prophylactic non-steroidal anti-inflammatory drugs for the prevention of macular oedema after cataract surgery

  • Review
  • Intervention

Authors

  • Blanche X Lim,

    1. National University Health System, Department of Ophthalmology, Singapore, Singapore
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    • Joint first author

  • Chris HL Lim,

    1. Royal Melbourne Hospital, Department of Ophthalmology, Melbourne, Victoria, Australia
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    • Joint first author

  • Dawn K Lim,

    1. National University Health System, Department of Ophthalmology, Singapore, Singapore
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    • Joint first author

  • Jennifer R Evans,

    1. London School of Hygiene & Tropical Medicine, Cochrane Eyes and Vision, ICEH, London, UK
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  • Catey Bunce,

    1. Kings College London, Department of Primary Care & Public Health Sciences, London, UK
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  • Richard Wormald

    Corresponding author
    1. London School of Hygiene & Tropical Medicine, Cochrane Eyes and Vision, ICEH, London, UK
    2. NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, Research and Development Department, London, UK
    • Richard Wormald, Cochrane Eyes and Vision, ICEH, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. r.wormald@ucl.ac.uk.

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Abstract

Background

Macular oedema (MO) is the accumulation of extracellular fluid in the central retina (the macula). It may occur after cataract surgery and may give rise to poor visual outcome, with reduced visual acuity and distortion of the central vision. MO is often self-limiting with spontaneous resolution, but a small proportion of people with chronic persistent MO may be difficult to treat. Chronic oedema may lead to the formation of cystic spaces in the retina termed 'cystoid macular oedema' (CMO). Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in cataract surgery and may reduce the chances of developing MO.

Objectives

The aim of this review is to answer the question: is there evidence to support the prophylactic use of topical NSAIDs either in addition to, or instead of, topical steroids postoperatively to reduce the incidence of macular oedema (MO) and associated visual morbidity.

Search methods

We searched a number of electronic databases including CENTRAL, MEDLINE and Embase. Date last searched 2 September 2016.

Selection criteria

We included randomised controlled trials (RCTs) in which adult participants had undergone surgery for age-related cataract. We included participants irrespective of their baseline risk of MO, in particular we included people with diabetes and uveitis. We included trials of preoperative and/or postoperative topical NSAIDs in conjunction with postoperative topical steroids. The comparator was postoperative topical steroids alone. A secondary comparison was preoperative and/or postoperative topical NSAIDs alone versus postoperative topical steroids alone.

Data collection and analysis

Two review authors independently selected studies for inclusion, assessed risk of bias and extracted data using standard methods expected by Cochrane. We pooled data using a random-effects model. We graded the certainty of the evidence using GRADE and considered the following: risk of bias of included studies, precision of the effect estimate, consistency of effects between studies, directness of the outcome measure and publication bias.

Main results

We identified 34 studies that were conducted in the Americas, Europe, the Eastern Mediterranean region and South-East Asia. Over 5000 people were randomised in these trials. The majority of studies enrolled one eye per participant; a small subset (4 trials) enrolled a proportion of people with bilateral surgery. Twenty-eight studies compared NSAIDs plus steroids with steroids alone. Six studies compared NSAIDs with steroids. A variety of NSAIDs were used, including ketorolac, diclofenac, nepafenac, indomethacin, bromfenac, flurbiprofen and pranopfen. Follow-up ranged from one to 12 months. In general, the studies were poorly reported. We did not judge any of the studies at low risk of bias in all domains. Six studies were funded by industry, seven studies were funded from non-industry sources, and the rest of the studies did not report the source of funding.

There was low-certainty evidence that people receiving topical NSAIDs in combination with steroids may have a lower risk of poor vision due to MO at three months after cataract surgery compared with people receiving steroids alone (risk ratio (RR) 0.41, 95% confidence interval (CI) 0.23 to 0.76; eyes = 1360; studies = 5; I2 = 5%). We judged this to be low-certainty evidence because of risk of bias in the included studies and indirectness, as the extent of visual loss was not always clear. Only one study reported poor vision due to MO at 12 months and we judged this to be very low-certainty evidence as there were only two events. Quality of life was only reported in one of the 34 studies comparing NSAIDs plus steroids versus steroids alone, and it was not fully reported, other than to comment on lack of differences between groups. There was evidence of a reduced risk of MO with NSAIDs at three months after surgery, but we judged this to be low-certainty due to risk of bias and publication bias (RR 0.40, 95% CI 0.32 to 0.49; eyes = 3638; studies = 21). There was inconsistent evidence on central retinal thickness at three months (I2 = 87%). Results ranged from -30.9 µm in favour of NSAIDs plus steroids to 7.44 µm in favour of steroids alone. Similarly, data on best corrected visual acuity (BCVA) were inconsistent, but nine out of 10 trials reporting this outcome found between-group differences in visual acuity of less than 0.1 logMAR.

None of the six studies comparing NSAIDs alone with steroids reported on poor vision due to MO at three or 12 months. There was low-certainty evidence that central retinal thickness was lower in the NSAIDs group at three months (mean difference (MD) -22.64 µm, 95% CI -38.86 to -6.43; eyes = 121; studies = 2). Five studies reported on MO and showed a reduced risk with NSAIDs, but we judged this evidence to be of low-certainty (RR 0.27, 95% CI 0.18 to 0.41; eyes = 520). Three studies reported BCVA at three months and the results of these trials were inconsistent, but all three studies found differences of less than 0.1 logMAR between groups.

We did not note any major adverse events - the main consistent observation was burning or stinging sensation with the use of NSAIDs.

Authors' conclusions

Using topical NSAIDs may reduce the risk of developing macular oedema after cataract surgery, although it is possible that current estimates as to the size of this reduction are exaggerated. It is unclear the extent to which this reduction has an impact on the visual function and quality of life of patients. There is little evidence to suggest any important effect on vision after surgery. The value of adding topical NSAIDs to steroids, or using them as an alternative to topical steroids, with a view to reducing the risk of poor visual outcome after cataract surgery is therefore uncertain. Future trials should address the remaining clinical uncertainty of whether prophylactic topical NSAIDs are of benefit, particularly with respect to longer-term follow-up (at least to 12 months), and should be large enough to detect reduction in the risk of the outcome of most interest to patients, which is chronic macular oedema leading to visual loss.

Plain language summary

Prophylactic non-steroidal anti-inflammatory drugs (NSAIDs) for the prevention of macular oedema after cataract surgery

What is the aim of this review?
The aim of this Cochrane Review was to find out if NSAID eye drops can prevent a sight-threatening complication of cataract surgery (swelling at the back of the eye, known as macular oedema). Cochrane researchers collected and analysed all relevant studies to answer this question and found 34 studies.

Key messages
There is only low-certainty evidence to support the use of NSAID eye drops to prevent macular oedema affecting vision after cataract surgery.

What was studied in the review?
There is a clear lens in the eye that focuses the light on the back of the eye. As people get older this lens can become cloudy. A cloudy lens is known as a cataract. Doctors can remove the cataract and replace it with an artificial lens. This is usually a very successful operation. Occasionally, people having cataract surgery can get swelling at the back of the eye after the operation. This swelling is known as macular oedema. It usually gets better on its own accord, but if it persists it can result in poor vision.

NSAIDs are a medication that can treat inflammation. They may be able to reduce the chances of this swelling happening. The NSAIDs studied in this review were eye drops.

What are the main results of the review?
The review authors found 34 relevant studies. These studies were conducted in all parts of the world including the Americas, Europe, the Eastern Mediterranean region and South-East Asia. Most (28) of these studies compared NSAIDs combined with steroids against steroids alone. Some of the studies (6) compared NSAIDs with steroids alone. A variety of NSAIDs were used, including ketorolac, diclofenac, nepafenac, indomethacin, bromfenac, pranopfen and flurbiprofen. People taking part in these trials were followed up from between one and 12 months. Most studies only followed up to two months or less. Six studies were funded by industry; seven studies were funded from non-industry sources and the rest of the studies did not report the source of funding.

There was low-certainty evidence that NSAIDs reduce the chance of poor vision due to macular oedema three months after cataract surgery. Only one study reported on poor vision due to macular oedema at 12 months and we judged this to have very low-certainty of evidence.

Using NSAIDs was associated with a reduced risk of macular oedema but the review authors judged this to be low-certainty.

Inconsistent results were seen for some measurements of macular oedema, such as the thickness of the tissue at the back of the eye (central retinal thickness) at three months after surgery. This measurement was not reported by any studies at 12 months after surgery.

Similarly, inconsistent results were seen for vision measurement (visual acuity) but most studies found small differences between people given NSAIDs and people not given NSAIDs.

Only one study reported quality of life, and this suggested little impact of NSAIDs on quality of life.

Adverse events mainly consisted of a burning or stinging sensation.

How up-to-date is this review?
The review authors searched for studies that had been published up to 2 September 2016.

Резюме на простом языке

Профилактическое применение местных нестероидных противовоспалительных средств (НПВС) для предотвращения макулярного отёка после хирургии катаракты

Какова цель этого обзора?
Целью этого Кокрейновского систематического обзора было найти доказательства о том, могут ли глазные капли с НПВС предотвратить угрозу потери зрения после хирургии катаракты (отёк в самом центре сетчатки - задней части глаза, который называется макулярным отёком) Для ответа на этот вопрос исследователи Кокрейн отобрали и проанализировали 34 клинических исследования.

Ключевые выводы
Существует низкий уровень доказательств, подтверждающих эффективность применения капель, содержащих НПВС, в отношении предотвращения макулярного отёка после операции по поводу катаракты.

Что изучалось в этом обзоре?
Прозрачный хрусталик фокусирует свет в центре сетчатки глаза. У пожилых людей хрусталик со временем может мутнеть и становиться менее прозрачным (мутным). Мутный хрусталик - это катаракта. Доктор удаляет катаракту и заменяет хрусталик искусственной линзой. Практически всегда операция проходит успешно. Иногда у людей, которые перенесли операцию по поводу катаракты и имплантации искусственного хрусталика, может возникнуть отёк в центре сетчатки глаза. Этот отёк называется макулярным отёком. Как правило, это преходящее состояние (разрешается само по себе), но если оно продолжается, это может привести к ухудшению зрения.

НПВС это лекарства, которые могут лечить воспаление. Они, может быть, способны снизить риск возникновения макулярного отёка. В этом обзоре изучались НПВС в виде глазных капель.

Каковы основные результаты этого обзора?
Авторы нашли 34 соответствующих исследования. Исследования были проведены во всех частях мира, включая Америку, Европу, Восточное Средиземноморье и Юго-Восточную Азию. Большинство (28) из этих исследований изучали эффект НПВС вместе с применением стероидов в сравнении с изолированным применением стероидов. Некоторые исследования (6) сравнивали эффект НПВС с эффектом стероидов "в одиночку". Были использованы различные НПВС в виде глазных капель: кеторолак, диклофенак, непафенак, индометацин, бромфенак, пранопфен и флурбипрофен. Люди, которые принимали участие в этих испытаниях, находились под наблюдением от одного до 12 месяцев. В большинстве исследований срок наблюдения был 2 месяца или меньше. Шесть исследований были профинансированы компанией-производителем (индустрией), семь - имели финансовую поддержку из не-индустриальных источников. В оставшихся исследованиях (21) не было указано об источнике финансирования.

Имеется низкое качество доказательств в отношении снижения риска ухудшения зрения вследствие макулярного отёка через 3 месяца после хирургии катаракты. Только в одном исследовании из 34 сообщалось о сниженном зрении из-за макулярного отёка на 12-м месяце после операции, и таким образом, мы решили, что это доказательства очень низкого качества (определенности).

Использование глазных капель с НПВС, возможно, связано со снижением риска возникновения макулярного отёка после хирургии катаракты, однако авторы обзора оценили эти доказательства как низкого качества (уверенности).

Противоречивые результаты были получены для некоторых клинических исследований с измерением толщины сетчатки с макулярным отёком на третий месяц после операции. Подобные измерения не были описаны ни в одном из исследований к 12 месяцу после операции.

Похожие противоречивые результаты были получены и в отношении измерения остроты зрения, однако в большинстве исследований была установлена незначительная разница в остроте зрения между группами людей, которые применяли и не применяли НВПС-капли.

Только одно исследование из 34 опубликовало результаты влияния НПВС-капель на качество жизни, поэтому сделан вывод о незначительном влиянии на качество жизни.

Побочные эффекты применения НПВС-капель главным образом заключались в жжении и покалывании.

Какова актуальность этого обзора?
Авторы включили в этот обзор исследования, которые были опубликованы по 2 сентября 2016-го года.

Заметки по переводу

Перевод: Арсланов Глеб Маратович. Редактирование: Зиганшина Лилия Евгеньевна. Координация проекта по переводу на русский язык: Cochrane Russia - Кокрейн Россия (филиал Северного Кокрейновского Центра на базе Казанского федерального университета). По вопросам, связанным с этим переводом, пожалуйста, обращайтесь к нам по адресу: cochrane.russia.kpfu@gmail.com; cochranerussia@kpfu.ru