Agentes antiinflamatorios no esteroideos tópicos para el edema macular cistoide diabético
Resumen
Antecedentes
El edema macular cistoide (EMC) diabético es un trastorno que incluye la acumulación de líquido en la porción interna de la retina. A menudo es posterior a los cambios en los vasos sanguíneos retinianos que dan lugar a que el líquido salga de los vasos. Aunque puede ser asintomático, los síntomas son principalmente la pérdida indolora de la visión central, a menudo con la molestia de ver manchas negras delante del ojo.
Se informa que el EMC puede resolverse espontáneamente, o fluctuar durante meses, antes de causar la pérdida de la visión. Si no se trata o no se diagnostica, la progresión del EMC puede dar lugar a la pérdida permanente de la visión.
Se ha observado que los pacientes con retinopatía diabética presentan marcadores inflamatorios elevados, y por lo tanto es probable que la inflamación ayude a la progresión de la vasculopatía en estos pacientes. Por lo tanto, también se han utilizado varios fármacos antiinflamatorios no esteroides (AINE) tópicos como ketorolac 0,5%, bromfenac 0,09% y nepafenac 0,1% de forma tópica para el tratamiento del EMC diabético crónico. En consecuencia, esta revisión se realizó para determinar los efectos de los AINE tópicos en el EMC diabético.
Objetivos
Evaluar los efectos de los fármacos antiinflamatorios no esteroides (AINE) tópicos para el edema macular cistoide (EMC) diabético.
Métodos de búsqueda
Se hicieron búsquedas en: CENTRAL (que contiene el registro de ensayos del Grupo Cochrane de Trastornos de los Ojos y la Visión [Cochrane Eyes and Vision Group]) (2014, número 12), Ovid MEDLINE, Ovid MEDLINE In‐Process and Other Non‐Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (enero 1946 hasta enero 2015), EMBASE (enero 1980 hasta enero 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (enero 1982 hasta enero 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) y la WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). No se aplicaron restricciones de fecha o idioma en las búsquedas electrónicas de ensayos. La última búsqueda en bases de datos electrónicas se realizó el 12 de enero de 2015.
Criterios de selección
Ensayos controlados aleatorios (ECA) y ensayos controlados cuasialeatorios que investigaban los efectos de los AINE aplicados de forma tópica en el tratamiento de los pacientes con EMC diabético a partir de los 18 años de edad.
Obtención y análisis de los datos
Dos autores de la revisión evaluaron de forma independiente la elegibilidad de los ensayos y examinaron todos los títulos y resúmenes disponibles para la inclusión. No hubo discrepancias y no fue necesario contactar con los investigadores de los ensayos para obtener datos faltantes.
Resultados principales
No se identificó ningún ECA que cumpliera los criterios de inclusión para esta revisión.
Conclusiones de los autores
La revisión no identificó ningún ECA que investigara los efectos de los AINE tópicos en el tratamiento del EMC diabético. La mayoría de los estudios identificados mediante las búsquedas electrónicas se habían realizado para analizar el efecto de los AINE tópicos para el EMC pseudofáquico. A falta de pruebas de alta calidad, los médicos deben utilizar su juicio clínico y otras pruebas de bajo nivel, como los ensayos observacionales no aleatorios, para decidir sobre el uso de AINE tópicos en los casos de EMC diabético.
Se necesita más investigación para comprender mejor la causa de este trastorno y su fisiopatología. Esta revisión sistemática ha identificado la necesidad de ECA bien diseñados, con el poder estadístico suficiente para evaluar los posibles efectos beneficiosos y adversos de los AINE tópicos en los pacientes con EMC diabético. Los ensayos futuros deben procurar incluir un tamaño de la muestra grande con un período de seguimiento suficiente de hasta un año.
PICO
Resumen en términos sencillos
Agentes antiinflamatorios no esteroideos tópicos para el edema macular cistoide diabético
Pregunta de la revisión
Se examinaron las pruebas acerca del efecto de los fármacos antiinflamatorios no esteroides para el edema macular cistoide diabético.
Antecedentes
La retinopatía diabética es una causa frecuente de ceguera en adultos de entre 20 y 74 años de edad. La causa principal de deficiencia de la visión en los pacientes con retinopatía diabética es la acumulación de líquido en la parte central de la retina (mácula) conocido como edema macular cistoide (EMC). El EMC es la variedad crónica y difusa del edema macular diabético (EMD). El uso de agentes antiinflamatorios tópicos se ha sugerido como un tratamiento potencial para el EMC diabético.
Se procuró examinar los ensayos controlados aleatorios (ECA) y los ensayos controlados cuasialeatorios (estudios de investigación clínica, que proporcionan pruebas de buena calidad sobre los efectos de las intervenciones) que investigaban los efectos de diversos fármacos antiinflamatorios no esteroides (AINE) aplicados de forma tópica para el tratamiento del EMC diabético, y evaluar si se observan beneficios significativos con los AINE tópicos.
Se examinaron las pruebas sobre el efecto de los preparados de AINE para ojos aplicados de forma local sobre la restauración de la visión en los pacientes con EMC diabético. Aunque se han usado diversos AINE tópicos para tratar el EMC diabético, a saber bromfenac 0,09%, nepafenac 0,1% y ketorolac 0,5%, no se encontró ningún ECA ni ensayo controlado cuasialeatorio que reuniera los requisitos para esta revisión. También se encontró que la mayoría de los estudios identificados mediante las búsquedas electrónicas se habían realizado para analizar el efecto de los AINE tópicos para el EMC pseudofáquico.
Se necesita más investigación para comprender los efectos de los AINE tópicos sobre el EMC diabético. Se recomienda la realización de un ECA para evaluar los efectos de los AINE tópicos en pacientes con EMC diabético. El ensayo necesitaría tener un seguimiento de al menos un año e incluir un tamaño de la muestra grande y un diseño consistente para evaluar cualquier efecto potencial beneficioso o adverso a largo plazo de los AINE aplicados de forma local.
Fecha de la búsqueda
Las pruebas están actualizadas hasta enero de 2015.
Authors' conclusions
Background
Description of the condition
Diabetes mellitus, especially Type 2, is escalating (Mokdad 2001) and is estimated to reach epidemic proportions around the world in the next 25 years (Bonow 2004). The prevalence of diabetes in adults worldwide was estimated at 4.0% in 1995 and is expected to rise to 5.4% by the year 2025 (Cockram 2000; King 1998). Diabetic retinopathy is a known complication of diabetes mellitus (Xiao‐Ling 2006), and is increasingly becoming a major cause of blindness throughout the world (Congdon 2003; Viswanath 2003).
Cystoid macular oedema (CMO) is a condition where accumulation of fluid occurs in the central part of the retina, largely due to capillary leakage. Although the most common cause of CMO is cataract surgery and other intraocular surgeries, it has also been observed in various other ocular conditions such as diabetic retinopathy, age‐related macular degeneration, uveitis, and eye injury etc. In diabetic CMO, the cystoid changes usually occur in cases of diffuse and chronic diabetic macular oedema (DMO) (Rotsos 2008).
Theories of the pathogenesis of CMO have looked at mechanical factors, such as tractional forces on the macula and disruption of the vitreoretinal interface (Rotsos 2008). However, the most accepted theory to date is vascular leakage and retinal oedema, initiated by the diffusion of mediators like prostaglandins being released in the eye (Scholl 2010). This theory is supported by evidence that cyclo‐oxygenase inhibitors reduce the incidence of angiographic CMO. Although natural history studies of pseudophakic CMO have shown that the majority of cases resolve spontaneously, one natural history study on diabetic CMO has shown the persistence of cystoid spaces, resulting in a severe decrease in visual acuity (Coscas 1984).
It is difficult to know the true incidence of CMO. Whilst subtle CMO is difficult to identify clinically, there may also be other factors that affect the accuracy of incidence estimates. New CMO is normally reported through the surgeon’s findings or via fluorescein angiography and optical coherence tomography.
Although CMO is often symptomatic in terms of visual impairment in either eye, it may be asymptomatic in some cases. It is reported that CMO may resolve spontaneously, or fluctuate for months before causing severe loss of vision, which often results in diminution of visual acuity to 20/200 level (Massin‐Korobelnik 1994). Fundoscopy usually shows an altered foveal reflex with a honeycomb appearance of the macula. In cases where the diagnosis of CMO is unclear, fundus fluorescein angiography may be used. The classical angiography picture is a 'flower petal' appearance at the macula. The amount of macular oedema can also be detected by a non‐invasive procedure called optical coherence tomography.
Various treatment options are available for diabetic CMO. The mainstays of treatment are grid photocoagulation (ETDRS 1987), intravitreal steroids (Grover 2008), vitrectomy (Otani 2002), and the most recent, intravitreal vascular endothelial growth factor (Haritoglou 2006).
Description of the intervention
Medical therapies for diabetic CMO have included two broad classes of agents: anti‐inflammatory drugs and agents with molecular targets (Boscia 2010). It has been found that patients with diabetic retinopathy have elevated inflammatory markers. Thus it is likely that inflammation aids in the progression of vascular disease in these patients (Ke 2000; Meleth 2005). Several topical non‐steroidal anti‐inflammatory drugs (NSAIDs) such as ketorolac 0.5%, bromfenac 0.09%, and nepafenac 0.1%, have also been used to treat chronic diabetic CMO. A Cochrane systematic review found two trials with topical ketorolac 0.5% ophthalmic solution that had a positive effect for treating chronic CMO following cataract surgery, and two trials that revealed no significant difference between the intervention and control groups (Sivaprasad 2005).
How the intervention might work
Topical NSAIDs are commonly prescribed in ophthalmic practice for their anti‐inflammatory property. In diabetic CMO, there is extracellular fluid accumulation and retinal oedema which is secondary to disruption of the blood retinal barrier (Gardner 2002). Studies have also demonstrated an association between CMO and inflammation mediated by prostaglandins (Bazan 1990; Miyake 2002; Scholl 2010). In the eye, prostaglandins are synthesised in the ciliary body and iris, causing vasodilatation and increasing vascular permeability with disruption of the blood‐ocular barrier with leukocyte migration, which results in oedema formation (Miyake 2002).
NSAIDs act as potent inhibitors for cyclo‐oxygenase enzymes, an active component of the inflammatory process involved in prostaglandin synthesis. When administered topically, NSAIDs achieve therapeutic levels in the aqueous humour, and are capable of a reduction in the synthesis of prostaglandins in the ciliary body and iris. More frequent administration of topical NSAIDs with longer duration of treatment leads to higher aqueous levels (Bucci 2007). Three topical NSAIDs, ketorolac 0.4%, bromfenac 0.09% and nepafenac 0.1% were proven to penetrate into the vitreous cavity, and ketorolac lowers the vitreous level of Prostaglandin E2 (PGE2) (Heier 2009) which is reportedly associated with vasodilatation and partial disruption of the blood‐ocular barrier (Quaranta 2013). It has been suggested that vasogenesis as well as vasogenic macular oedema can also be strategically controlled by administration of anti‐inflammatory drugs such as NSAIDs (Boscia 2010).
Why it is important to do this review
Diabetic retinopathy is found to be the most frequent cause of new cases of blindness in adults aged 20 to 74 years (Klein 1984). Diabetic CMO is one of the factors for severe vision impairment in patients with diabetic retinopathy. DMO is the leading cause of visual impairment that occurs with diabetic retinopathy (Girach 2007). Diabetic CMO is more commonly found where there is diffuse and chronic DMO.
As with most treatments mentioned earlier, however, there are limitations and risks, most notably their invasive nature. The use of a topical alternative would therefore be markedly safer and easier, if proven to be effective. A few studies have reported the beneficial effect of topical NSAIDs in treating diabetic CMO as well as DMO; however there is currently no available systematic appraisal of evidence of the safety and effectiveness of topical NSAIDs for cases of diabetic CMO. A systematic review would assist in analysing the effects of topical NSAIDs in reducing or resolving diabetic CMO.
Objectives
To assess the effects of topical non‐steroidal anti‐inflammatory drugs (NSAIDs) for diabetic cystoid macular oedema (CMO).
Methods
Criteria for considering studies for this review
Types of studies
We planned to include all randomised controlled trials (RCTs). We also planned to include quasi‐RCTs if evidence of effects (benefits or harms) could not be adequately studied in RCTs and only if there was sufficient evidence that intervention and control groups were similar at baseline.
Types of participants
We did not take into consideration gender and race when selecting trials, although participants had to be over the age of 18 years. We included participants that had diabetic CMO diagnosed clinically. We did not exclude from this review participants who were non‐responsive to previous treatment (i.e. photocoagulation).
Types of interventions
We planned to include trials where topical NSAIDs were compared to placebo, no treatment, and other modalities of treatment.
Types of outcome measures
Primary outcomes
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The primary outcome for this review was 2 or more lines improvement of visual acuity from baseline (Early Treatment Diabetic Retinopathy Study (ETDRS), Snellen or LogMAR equivalent) at three months of treatment.
Secondary outcomes
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Proportion of participants showing improvement in central retinal thickness, measured with optical coherence tomography after three months of treatment, as a continuous outcome.
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Proportion of participants showing persistence of subretinal fluid with optical coherence tomography after three months of treatment as a dichotomous outcome.
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Proportion of participants showing improvement in fundus fluorescein angiography findings after three months of treatment. (Improvement is defined by decreased leakage in fundus fluorescein angiography).
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Quality of life: we planned to summarise the data on quality of life by any validated measure (such as National Eye Institute 25‐item Visual Function Questionnaire (NEI VFQ‐25) and Impact of Visual Impairment (IVI) Questionnaire) when found to be reported in the included studies.
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Adverse outcomes: we planned to tabulate all adverse effects related to topical application of NSAIDs for the treatment of diabetic CMO that are found to be reported in the included studies.
Search methods for identification of studies
Electronic searches
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 12), Ovid MEDLINE, Ovid MEDLINE In‐Process and Other Non‐Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to January 2015), EMBASE (January 1980 to January 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to January 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 12 January 2015.
See: Appendices for details of search strategies for CENTRAL (Appendix 1), MEDLINE (Appendix 2), EMBASE (Appendix 3), LILACS (Appendix 4), ISRCTN (Appendix 5), ClinicalTrials.gov (Appendix 6) and the ICTRP (Appendix 7).
Searching other resources
We handsearched the International Congress of Ophthalmology from 1990 onwards until the last congress in 2012 to identify unpublished studies. We contacted organisations and researchers in the field of ophthalmology, and pharmaceutical companies for information on current trials. We also checked the reference lists of all trials identified by the above methods.
Data collection and analysis
Selection of studies
Two review authors (SS, KT) independently assessed trial eligibility and screened all available titles and abstracts for inclusion. If relevant data from the abstract were difficult to ascertain, the full‐text of the report was retrieved. Two review authors (SS, KT) assessed the eligibility criteria independently by filling‐in the eligibility form that was designed in accordance with the inclusion criteria. The review authors were unmasked to the trial authors, institutions and trial results during their assessments. If a disagreement occurred, they were solved by discussion, or if required, a third review author (AH) was asked to express his view.
As no trials met our inclusion, we will follow the steps below for future updates.
Data extraction and management
Two review authors (SS, KT) planned to independently extract data for primary and secondary outcomes onto paper data collection forms developed by the Cochrane Eyes and Vision Group. The same two authors then planned to share the responsibility of entering the data into Review Manager 5 (RevMan 2014) and a third author (AN) planned to check for errors and inconsistencies. We planned to resolve any differences in data extraction by discussion and consensus.
We planned to use a standard data extraction form which will include at least the following items.
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Method: duration, way of randomisation, allocation concealment method, masking, country, and setting.
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Participants: type of sampling, number in comparison group, age, sex, similarity of group at base line, and losses to follow‐up with reason.
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Interventions: placebo will be included, interventions (dose, route and duration), comparison intervention (dose, route and duration), and co‐medication (dose, route and duration).
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Outcomes: outcomes specified above, any other outcomes assessed, times of assessment, and length of follow‐up.
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Notes: published or unpublished data, title, authors, source, contact address, language of publication, year of publication, and funding sources if any.
Assessment of risk of bias in included studies
Two review authors (AB, AN) planned to independently assess the risk of bias of the included studies by using the criteria outlined in Chapter 8 of theCochrane Handbook for Systematic Reviews of Interventions (Higgins 2011a). We planned to resolve any disagreements by discussion or by the intervention of a third review author (SN).
We planned to assess the following five components for each of the trials: random sequence generation (selection bias); allocation concealment (selection bias); masking (blinding) of participants and personnel (performance bias), and masking of outcome assessment (detection bias); incomplete outcome data (attrition bias through withdrawals, drop outs and protocol deviations); and selective reporting bias. We also planned to assess other sources of bias as reported in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011a), such as bias related to the specific study design, early stoppage of trials, extreme baseline imbalance or whether the study appeared to have been fraudulent. For each of these components, we planned to assign one of the following risk of bias judgements: 'low risk' of bias, 'high risk' of bias, or ‘unclear risk’ for uncertain risk of bias. We planned to record the results in the standard table in Review Manager 5 (RevMan 2014), and to summarise the findings in a ‘Risk of bias' table or graph.
Measures of treatment effect
For data analysis, we planned to follow the guidelines set out in Chapter 9 of the Cochrane Handbook for Systematic Review of Interventions (Deeks 2011).
For dichotomous data such as improvement of 2 or more Snellen lines, persistence of subretinal fluid detected by optical coherence tomography, improvement in fundus fluorescein angiography and occurrence of adverse effects, we planned to present the results using risk ratios (RRs) and their 95% confidence intervals (CIs).
For continuous outcomes such as central retinal thickness and quality of life we planned to calculate mean difference (MD) if the outcomes were measured by the same scales within the included studies. If the same outcomes were measured by different scales, we planned to use standard mean difference (SMD) with 95% CIs.
Unit of analysis issues
In ophthalmic RCTs, the unit of analysis can be either the participant or the eye. If the unit of analysis is the eye, it can be one eye, two eyes or mixed. In two‐eyed studies, if both eyes received the same treatment, we considered these studies as clustered, and if both eyes received different treatments, they would be considered as paired. For each trial included, we planned to document the unit of analysis and study design. If included studies used different methods, we planned to estimate the treatment effect at the study level and perform meta‐analysis by using the inverse variance method.
Dealing with missing data
Where data are missing due to participant drop out, we planned to conduct a primary analysis based on participants with complete data. We consider that missing outcomes will not be a problem if loss to follow‐up is documented and judged to be unrelated to outcomes in both study arms, as per Chapter 16 of the Cochrane Handbook for Systematic Review of Interventions (Higgins 2011b). We planned to get full reports from authors where studies are either published in abstract form or presented at meetings. We planned to contact the primary investigator in case of missing data or unclear information in the study reports. We also planned to consider that missing outcome data are not a problem if the causes are well documented. However, if the causes of missing data are not available, we planned to document the possible effects of the missing participants through a sensitivity analysis.
Assessment of heterogeneity
We planned to use the Chi2 test to assess statistical heterogeneity and considered P < 0.1 as statistically significant. To quantify the statistical heterogeneity, we planned to use forest plots and the I2 statistic. We planned to use the following guidelines for interpreting I2 values: 0% to 40% as insignificant heterogeneity, 30% to 60% as moderate heterogeneity, 50% to 90% as substantial heterogeneity, and 75% to 100% as considerable heterogeneity (Deeks 2011). We also planned to assess clinical and methodological heterogeneity by examining the characteristics and methodology section of individual studies.
Assessment of reporting biases
Three review authors (SS, KT, AH) carried out comprehensive searches to minimise publication and reporting biases, and they planned to consider the likelihood of these biases. Within studies, we planned to consider selective outcome reporting as part of the risk of bias assessment. We planned to compare the 'Methods' section of the fully published paper to the 'Results' section to ensure that all of the outcomes which were measured, were reported. We planned to assess possible publication bias by using funnel plots to explore the relationship between effect size and study size. We also planned to look at funnel plots only where we have sufficient trials i.e. 10 trials or more. We would visually examine them for symmetry, with greater symmetry indicating a lower risk of reporting bias.
Data synthesis
We planned to carry out statistical analysis using Review Manager 5 (RevMan 2014). If there are less than three studies, we would use a fixed‐effect model. If there is minimal statistical heterogeneity and if there is minimal clinical heterogeneity between the trials, we planned to combine the results in a meta‐analysis using a random‐effects model. If there is considerable heterogeneity (I2 statistic of 50% or more), we will discuss the results in narrative and tabulated form only. For identifying heterogeneity we would not only rely on the statistical significance of a Chi2 test, but also examine the results of the forest plot of the study. We planned to convert Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores to logMar for calculations and then use them in the meta‐analysis. If we find studies in which Snellen (decimal) visual acuity is measured by non‐ETDRS or non‐logarithmic charts, we would only extract data if calculations are based on logMar transformed data and then transformed back to decimals for reporting. If we find studies in which means and standard deviations (SDs) are computed using decimal visual acuity, we would not use them in the meta‐analysis but planned to summarise their results in the discussion.
Subgroup analysis and investigation of heterogeneity
We did not perform any subgroup analyses in this review.
Sensitivity analysis
We planned to carry out sensitivity analysis to investigate the robustness of the results regarding the various components of risk of bias. We also planned to examine the effect on the primary outcome of excluding any study judged to be at overall high risk of bias.
Summary of findings
We planned to create a ‘Summary of findings” table using GRADEpro software (version 3.6) (GRADEpro 2014) to assess parameters such as limitations of design, inconsistency, indirectness, imprecision and publication bias. In the table we planned to include all the available outcomes reported in the included studies.
Results
Description of studies
Results of the search
The electronic searches yielded a total of 294 references (Figure 1). The Trials Search Co‐ordinator scanned the search results, removed 55 duplicates and then removed 180 references which were not relevant to the scope of the review. We screened the remaining 59 reports but did not identify any RCTs that met the inclusion criteria for this review.
Results from searching for studies for inclusion in the review
Included studies
We did not identify any RCTs that met the inclusion criteria.
Excluded studies
We did not exclude any RCTs.
Risk of bias in included studies
We did not identify any eligible trials for inclusion in the review.
Effects of interventions
The searches did not identify any RCTs, or any ongoing trials for inclusion in this review.
Discussion
This review of topical non‐steroidal anti‐inflammatory drugs (NSAIDs) for diabetic cystoid macular oedema (CMO) failed to identify any randomised controlled trials (RCTs) or any ongoing trials for inclusion in this review. Most of the studies identified through the electronic searches had been conducted to analyse the effect of topical NSAIDs for pseudophakic CMO.
A case series study evaluating the effects of topical nepafenac 0.1% in six eyes with diabetic macular oedema (DMO) showed that there was significant reduction in average foveal thickness from 417 µm to 267 µm, with statistically significant improvement in mean visual acuity from 0.78 logMAR to 0.67 logMAR after a mean follow‐up period of 178 days (Callanan 2008).
Many studies have shown the benefits of single intravitreal injection of NSAIDs in DMO. A single dose of intravitreal diclofenac (500 µg/0.1 mL) in eyes with clinically significant macular oedema reported a prominent improvement in visual acuity (Soheilian 2010). Similar results were seen in two studies conducted in eyes with DMO refractory to laser photocoagulation (Maldonado 2011; Reis 2010) where intravitreal ketorolac (500 µg/0.1 mL and 3000 µg/0.1 mL) were given, respectively.
Summary of main results
This review failed to identify any published trials or ongoing studies from trial registers reporting the effects and safety of topical NSAIDs for treating diabetic CMO. Although some case series studies have suggested the benefit of topical NSAIDs in the treatment of diabetic CMO, the absence of definitive RCTs suggest that it is an area where more evidence is needed to inform the scientific community as to the benefits and risks of treating diabetic CMO with topical NSAIDs.
Agreements and disagreements with other studies or reviews
Diabetic CMO, a form of chronic CMO, is a challenge observed in patients with diabetic maculopathy which results in a severe impairment in visual acuity (Coscas 1984). Unfortunately, however, there are no RCTs; suggesting that evidence is needed for or against the use of topical NSAIDs in the affected population.
A Cochrane systematic review evaluating the effects of NSAIDs for treating pseudophakic CMO reported that topical ketorolac tromethamine 0.5% had a positive effect for treating chronic pseudophakic CMO (Sivaprasad 2012). Although diabetic CMO has similar pathophysiology with that of chronic CMO following cataract surgery, this evidence cannot be used as evidence for the effects of topical NSAIDs in diabetic CMO.
Results from searching for studies for inclusion in the review
