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Clinical Trials  |   March 2014
Randomized, Double-Blind, Placebo-Controlled Clinical Trial on the Efficacy of 0.5% Indomethacin Eye Drops in Uveitic Macular Edema
Author Affiliations & Notes
  • Pia Allegri
    Ophthalmology Department, Uveitis Tertiary Referral Center, Rapallo Hospital, Genova, Italy
  • Ugo Murialdo
    Ophthalmology Department, Uveitis Tertiary Referral Center, Rapallo Hospital, Genova, Italy
  • Simona Peri
    Pharmaceutical Department, Sestri Levante Hospital, Genova, Italy
  • Rosanna Carniglia
    Pharmaceutical Department, Sestri Levante Hospital, Genova, Italy
  • Maria Grazia Crivelli
    Pharmaceutical Department, Sestri Levante Hospital, Genova, Italy
  • Silvia Compiano
    Ophthalmology Department, Uveitis Tertiary Referral Center, Rapallo Hospital, Genova, Italy
  • Silvia Autuori
    Ophthalmology Department, Uveitis Tertiary Referral Center, Rapallo Hospital, Genova, Italy
  • Antonio Mastromarino
    Ophthalmology Department, Uveitis Tertiary Referral Center, Rapallo Hospital, Genova, Italy
  • Monia Zurria
    Reasearch and Development, Alfa Intes Industria Terapeutica Splendore, Casoria, Napoli, Italy
  • Giuseppina Marrazzo
    Reasearch and Development, Alfa Intes Industria Terapeutica Splendore, Casoria, Napoli, Italy
  • Correspondence: Pia Allegri, Uveitis Tertiary Referral Centre Head, Rapallo Hospital, Genova, Italy, Via San Pietro, 8, 16035 Rapallo, Genova, Italy; pallegri@asl4.liguria.it
Investigative Ophthalmology & Visual Science March 2014, Vol.55, 1463-1470. doi:10.1167/iovs.13-13202
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      Pia Allegri, Ugo Murialdo, Simona Peri, Rosanna Carniglia, Maria Grazia Crivelli, Silvia Compiano, Silvia Autuori, Antonio Mastromarino, Monia Zurria, Giuseppina Marrazzo; Randomized, Double-Blind, Placebo-Controlled Clinical Trial on the Efficacy of 0.5% Indomethacin Eye Drops in Uveitic Macular Edema. Invest. Ophthalmol. Vis. Sci. 2014;55(3):1463-1470. doi: 10.1167/iovs.13-13202.

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Abstract

Purpose.: The aim of the present randomized, double-blind, placebo-controlled clinical trial was to assess the efficacy and tolerability of 0.5% indomethacin (INDOM) eye drops in adult patients suffering from macular edema (ME) related to different etiology uveitis.

Methods.: Forty-six eyes of 31 adult patients (20 females and 11 males) mean age 39 years, affected by inflammatory ME, were randomized to receive a dose of commercial 0.5% INDOM eye-drops four times per day (16 subjects = 23 eyes) or placebo (the vehicle of INDOM, 15 subjects = 23 eyes) during a 6-month active therapy follow-up. Study assessment at each visit included visual acuity testing (VA), slit-lamp examination, IOP evaluation, and Heidelberg Spectralis optical coherence tomography (OCT) central foveal thickness (CFT) measurement. Any variation in subjective symptoms and tolerability was also detected.

Results.: Statistical analysis showed, from baseline to the 6-month visit, a significant reduction in CFT (P < 0.0001) and a significant improvement in VA only in the 0.5% INDOM-treated group; a global reduction of discomfort symptoms was present in both groups (P < 0.001).

Conclusions.: The four times per day administration of 0.5% INDOM eye drops in eyes affected with uveitic ME from different etiologies, compared with placebo, is associated with a significant reduction in ME at the 6-month follow-up visit, as measured by spectral-domain optical coherence tomography (SD-OCT). However, not all eyes showed a complete resolution of ME because of vitreoretinal traction. ( https://eudract.ema.europa.eu/index.html number, EUDRACT 2011-001522-20.)

Introduction
Macular edema (ME) is a frequent complication of uveitis (mainly intermediate, posterior, and pan-uveitis). 14 A common outcome related to ME is visual impairment. 2 In a recent large survey of Rothova, an important VA decrease (in more than 1/5 of the uveitic patients) was caused by cystoid ME (CME), and mainly in chronic forms of CME and in elderly subjects; a clinically significant CME developed in more than one-third of all the examined patients. 3  
Inflammatory ME is multifactorial and recognizes a variety of inducing mechanisms, among which is inner blood–retinal barrier inflammatory disruption, inflammation of retinal vessels or vasculitis, vitreous tractive syndrome, dysfunction of RPE and choroidal or choriocapillaris inflammation are the leading causes. 57  
The pathophysiology of uveitic CME is partially unknown and it is mainly related to damaged tissue inflammatory response with the activation of arachidonic acid cascade and the release of inflammatory mediators (prostaglandins, tromboxanes, leukotrienes, metalloproteinases, nitric oxide, interleukins, VEGF, TMNF-α, etc.) both from the cycloxygenase and lypoxygenase pathways. These inflammatory-derived substances induce a pathologic hyperpermeability of retinal vessel walls with consequently a fluid, protein, and other macromolecules extravasation into the retinal interstitium. Another recently discovered causal factor is the endothelial damage resulting from leukostasis (abnormal adherence of leukocytes to the vessel walls), which is mediated by inflammatory mediators. The complex of these mechanisms provokes the inner blood–retinal barrier loss of integrity, which is the most important recognized pathogenic mechanism leading to RPE pump, waste system, and metabolism failure, which results in fluid leakage into the outer plexiform layer at the macula. 810 Recent improvement in ophthalmologic diagnostic tools with the introduction of new generation Spectralis optical coherence tomography (OCT), gave ophthalmologists the chance to detect this underlying complication 1113 even when subclinical. 
A variety of treatment options targeting systemic and ocular inflammatory mediators showed their efficacy in improving visual acuity by the reduction of uveitic ME. 
Mainstay therapy for uveitic CME are systemic and topical corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs), which have shown their efficacy in the prophylaxis and treatment of inflammatory ME related to surgery or to uveitis. 1417 Topical NSAIDs block the cyclooxygenase enzymes and inhibit prostaglandin synthesis, thereby controlling the associated inflammation. 18,19  
Local anti-inflammatory therapy may be associated with systemic carbonic anhydrase inhibitors (acetazolamide) and/or with oral steroids. 
Other therapeutic options for recalcitrant and resistant cases of uveitic ME are posterior sub-Tenon corticosteroid injections, systemic corticosteroids (intravenous followed by oral administration), intravitreal steroids, and anti-VEGF drugs, intravitreal delivery steroid systems, systemic (or intravitreal) steroid-sparing immunosuppressive drugs (the most used of which are methotrexate, cyclosporine A, azathioprine, and mycophenolate mofetil), interferon-α (and in multiple sclerosis-associated uveitic CME, and interferon-β), somatostatin analogues (octreotide-LAR), and systemic or intravitreal biologic drugs (mainly anti-TNFα agents). 2025  
Vitrectomy plays a role when an uveitic CME caused by vitreomacular traction is present. 26,27  
The aim of the present randomized, double-blind, placebo-controlled clinical trial was to assess the efficacy and tolerability of 0.5% indomethacin (INDOM) eye drops in adult patients affected by uveitic ME. 
Materials and Methods
The present work is a prospective, randomized, double-blind, with paired groups, controlled with placebo, study (EUDRACT 2011-001522-20), including 46 eyes of 31 patients (20 females and 11 males), affected by inflammatory uveitic ME in one or both eyes. These numbers are related to the eyes/subjects who fully completed the 6-month follow-up. 
The total number of included subjects was 43 (68 eyes), but 12 patients were lost during the follow-up period; five patients (eight eyes) were not compliant to the scheduled protocol, and seven patients (14 eyes) were excluded because during the follow-up period they required a rescue treatment in relation to the worsening of visual acuity and/or of inflammatory CME (four subjects underwent systemic immunosuppressive treatment with mycofenolate mofetil, in association with oral steroids, and three patients underwent interferon α-2a in association with systemic steroids and immune suppressants). 
Patients were randomized to continuously receive 0.5% INDOM eye drops (INDOM; Intes Industria Terapeutica Splendore, Naples, Italy) four times per day (QID) (Group B), or placebo (the vehicle of INDOM, Group A) during a 6-month (+20 days) period treatment. Table 1 shows the baseline characteristic of both groups. 
Table 1
 
Demographic and Clinical Characteristics
Table 1
 
Demographic and Clinical Characteristics
Group A, n = 16 (23 Eyes) Group B, n = 15 (23 Eyes) P Value
Age, y 59 ± 19.03 65.69 ± 11.27 0.10
Sex, male/female 6/9 5/11 0.61
Central foveal thickness at baseline, μm 390.6 ± 162.3 446.0 ± 149.4 0.11
Global discomfort index at baseline 1.08 ± 0.90 1.04 ± 0.7 0.81
The study inclusion criteria was age over 18 years, both sexes, any race, any kind of uveitis complicated by OCT-detected ME, subjects able to give informed consent, to actively participate in the scheduled visits of the study, and not included in other clinical studies. 
The exclusion criteria included age under 18 years, participation in another study, positive history for recent (6 months previously) ocular trauma, ocular surgery, ocular herpes or other kinds of inflammatory or infective disease of the eye and its adnexa, diabetic retinopathy, glaucoma, recent (3 months before) intravitreal treatment, exfoliative syndrome, active peptic ulcer, severe liver or renal impairment, uncontrolled asthma, chronic systemic treatment with NSAIDs, mono-ocularity, pregnancy or breast feeding, and any intolerance or known hypersensitivity to the study drug or to other NSAIDs. In the end, 31 subjects were selected to participate in this study. 
The detected causes of inflammatory ME are summarized in Table 2. In particular, we found in 23 eyes (50%) of 15 patients, intermediate uveitis of sarcoid, idiopathic, demyelinating origin; in 17 eyes (37%) of 10 subjects, autoimmune retinal vasculitis derived from rheumatoid arthritis or related conditions, Crohn's disease and sarcoidosis; in three eyes (6.5%) of three patients, post infective (one Lyme disease, one Varicella Zoster Virus infection, one Toxoplasmosis) retinal vasculitis; in three eyes (6.5%) of three different patients, HLA B27 + related anterior uveitis. 
Table 2
 
Main Causes of Inflammatory Macular Edema
Table 2
 
Main Causes of Inflammatory Macular Edema
Type of Uveitic CME Eyes N (%) Patients N (%)
Intermediate uveitis 23 (50) 15 (48.4)
Retinal vasculitis 17 (37) 10 (32)
Postinfective uveitis 3 (6.5) 3 (9.8)
HLA B27/anterior uveitis 3 (6.5) 3 (9.8)
Total 46 (100) 31 (100)
In all the included eyes, we ruled out the presence of an active (Herpetic, Toxoplasmic, or Borrelia Burgdoferi–related) infection by means of aqueous PCR examination; the three postinfective CME cases were PCR-negative, and were considered as immune-related uveitis. 
Acute (not present at previous check-ups) OCT-detected inflammatory ME was the only selection criteria. 
Concomitant ongoing systemic treatments with steroids (prednisone), immune-suppressants (azathioprine, methotrexate, cyclosporine, and mycophenolate mofetil), and biologicals (infliximab, adalimumab, and rituximab) were recorded at each visit and, during the 6-month period study, were not modified. 
Local treatment with mydriatic (1% tropicamide or 0.5% atropine) or steroid (0.2% dexamethasone) eye drops to treat occurring acute anterior uveitis was permitted only for 2 weeks at a 5-day tapered dose (from QID) and only twice during the 6-month protocol. 
Patients were selected from November 2011 until July 2012 in Rapallo Hospital, Tertiary Referral Uveitis Centre (Geneva, Italy) and over a period of approximately 180 days, subjects included into the study were scheduled to undergo four study visits: at baseline (V0), at 30 + 3 days (V1), at 90 + 10 days (V2), and at 180 + 20 days (V3). 
Study assessments at each visit included accurate history and evaluation of inclusion/exclusion criteria if any change had occurred during the trial, visual acuity (VA) testing (Sloan decimal scale), anterior segment slit-lamp examination, fluorescein staining for corneal epithelial damage or dry eye evidence, IOP measurement (Goldmann applanation tonometry), pupil dilated fundus examination, OCT (HRA+OCT Heidelberg Spectralis; Heidelberg Engineering, Heidelberg, Germany) to assess CFT (μm). 
To test VA, we used the VA electronic optotype (Vista Vision Wide Iris; DMD MED TECH, Villarbasse, Italy) and to uniform results we used the Sloan 5 letters optotype (the registered decimal value matches to the line where at least three letters were correctly read). 
Central macular thickness (fovea center) was appraised by Spectralis HRA+OCT instrument (Heidelberg Engineering) and the T0 value (in μ) was compared with the following measurements by using the “follow-up” program of the instrument. We took as normal CFT, the value of 280 μ + 20 μ, as written in recent literature. 2830  
General history investigation, included local or systemic allergy, systemic hypertension or cardiovascular diseases, respiratory system, liver, metabolism diseases, and recent surgery (up to 1 year before). Ocular history survey included dry-eye syndrome, glaucoma, recent trauma or surgery, lid, conjunctiva, and cornea diseases. 
Before beginning the study, all patients were required to provide written informed consent and the study was approved without any change by the Rapallo Hospital ethical committee and was conducted following Helsinki Declaration guidelines. 
Eye drops were administered to patients in the single dose formulation (0.5 mL) in a strip containing 10 single unit dose preservative-free eye drops, again contained in a large box of 10 blisters (for a total of 100 single-use eye drop bottles). Each single dose bottle contained 0.5% INDOM for Group B patients or an artificial tear (vehicle of INDOM for Group A). The latter product was a methyl-hydroxy-propyl-cellulose “4000,” monobasic and dibasic sodium phosphate, chloride sodium, edetate sodium, and purified water mixture, used also as an artificial tear substitute. 
Patients who met the inclusion/exclusion criteria, were randomized in a 1:1 ratio to instill one drop QID either 0.5% INDOM or vehicle eye drops for a period of approximately 6 months. Allocation of therapy was determined by a unified randomization table provided by the company (Intes Industria Terapeutica Splendore) to the investigator. Both kinds of eye drops were labeled identically and divided into group A and group B boxes. 
A questionnaire about treatment tolerance and agreement was given to all the subjects and at each control visit any variation was recorded. The questionnaire, included in a range from 0 to 3 (0 none; 1 mild; 2 moderate; 3 severe), main symptoms such as tearing, itching, photophobia, burning, and global discomfort sensation. 
Primary efficacy end-point was CFT reduction, detected by testing the differential value between day 0 and 180 days after treatment. 
Statistical Analysis
Statistical analysis on differences between baseline and 30, 90, and 180 days after treatment for CFT and VA was carried out with repeated measures analysis with clustered subject (or nested model procedure) because it is useful to correlate subjects in which only one or both eyes were treated. 
To evaluate the primary efficacy end-point (change in foveal thickness during the treatment time) the Bonferroni correction has been used and χ2 test was used to test secondary parameters of efficacy. 
Variability in adherence across age quartiles (Table 3) were evaluated using a Fisher's exact test. A P value less than or equal to 0.05 was considered as statistically significant. 
Table 3
 
Age Categorized by Quartiles
Table 3
 
Age Categorized by Quartiles
Min First Quartile (Q1) Median (Q2) Third Quartile (Q3) Max
Group (A+B) 22 53 62.35 ± 15.83 75 83
Group A 22 38 59 ± 19.03 75 83
Group B 38 60 65.7 ± 11.27 75 80
In summary, this clinical trial is designed to detect a difference between randomly assigned treatment groups considered during the time as primary parameter of efficacy CFT from baseline to the end of follow-up, 6 months after treatment. Sample size calculations estimated that enrollment of less than 50 patients would provide 80% power to detect this difference, allowing for a type one error probability of 0.05 (α = 0.05), assuming 10% losses to follow-up. 
Statistical analysis was carried out using Fisher's exact test to evaluate other data such as connection between age and treatment, different diagnosis, and treatment, sex- and treatment-related differential diagnosis. 
Results
Two topical treatments, A (placebo) and B (0.5% INDOM), were analyzed in a randomized, double-blind, placebo-controlled study to evaluate the efficacy of 0.5% INDOM eye drops QID for 6 months (+20 days) in the treatment of inflammatory acute ME deriving from different forms of uveitis. 
Statistical analysis showed a CFT significant reduction only in Group B patients and it was relevant after 90 days of treatment (P < 0.001) only. No essential differences or a slight worsening was observed in Group A patients during the time (Fig. 1A, shows a spectral domain-OCT [SD-OCT] of two group A and group B representative patients, before and after treatment; Fig. 1B shows that the 0.5% INDOM-treated eyes had a progressive decrease in central thickness). In one patient of Group B, who suffered from sarcoid vasculitic ME, the presence of an epiretinal membrane, despite 0.5% INDOM treatment, showed the persistence of ME and the evolution toward a foveal hole. 
Figure 1
 
(A) Optical coherence tomography analysis from two representative patients from group A and B before and after treatment. (B) Central foveal thickness recorded in group A and group B during the follow-up period. **P < 0.001 versus baseline; §P < 0.0001 versus Group A at 180 days after treatment.
Figure 1
 
(A) Optical coherence tomography analysis from two representative patients from group A and B before and after treatment. (B) Central foveal thickness recorded in group A and group B during the follow-up period. **P < 0.001 versus baseline; §P < 0.0001 versus Group A at 180 days after treatment.
Visual acuity analysis showed a proportional improvement during time (P < 0.001) in Group B patients (Fig. 2) only. 
Figure 2
 
Visual acuity in decimal scale. **P < 0.001; ***P < 0.0001 versus baseline, no significant differences have been observed in group A patients.
Figure 2
 
Visual acuity in decimal scale. **P < 0.001; ***P < 0.0001 versus baseline, no significant differences have been observed in group A patients.
None of the study subjects interrupted local therapy at any time (because of local or systemic side effects) and/or modified local or systemic anti-inflammatory or immunosuppressive therapy. 
Although INDOM-treated subjects were older than placebo-treated subjects, statistical analysis showed no significance (Fisher test: P = 0.3481). 
Visual acuity (Fig. 2) showed a statistically significant improvement in the treated group and a significant ratio time-treatment from baseline to 6 months after treatment, in the treated group only (average in decimals: 0.4 at day 0 to 0.56 at day 180) (P < 0.0001). No differences have been observed in VA of placebo-treated patients (average: 0.52 at day 0 and 0.55 at day 180. 
Correlation between VA and CFT showed statistical evidence (P < 0.001) from baseline to end of study value when analysis was carried out directly from V0 to V3; a poor statistical significance was present between intermediate measurements and baseline. 
Statistical evaluation of symptoms during the follow-up time showed a global reduction of dry-eye or discomfort symptoms in both groups (P < 0.001) when compared from day 0 with the end of treatment (Table 4). 
Table 4
 
Average Values of the Subjective Symptoms During the Time Course of the Treatment (Score: 0–3)
Table 4
 
Average Values of the Subjective Symptoms During the Time Course of the Treatment (Score: 0–3)
Baseline 30 d 90 d 180 d
Tearing
 Group A 0.7391 0.5217 0.3913 0.1304
 Group B 0.7391 0.6522 0.3478 0.1739
Burning sensation
 Group A 0.6522 0.3913 0.1304 0.1304
 Group B 0.8261 0.5652 0.3478 0.2609
Photophobia
 Group A 0.6957 0.5652 0.3478 0.1304
 Group B 0.6522 0.5652 0.4348 0.1739
Itching
 Group A 0.8261 0.4348 0.2174 0.1304
 Group B 0.7391 0.7826 0.4783 0.3043
Global discomfort index
 Group A 1.0870 0.4348 0.2174 0.1304
 Group B 1.0435 0.7826 0.6087 0.3478
Discussion
Our study was aimed at assessing the efficacy of 0.5% INDOM single dose eye drops on inflammatory ME complicating different forms of uveitis and one of the common causes of visual impairment. 
We included in our study a homogeneous group of eyes affected with CME of immune-mediated or auto-immune origin and excluded, by means of aqueous PCR, any active infection. 
The current normal standard of care for ME as a severe uveitic complication includes the use, often in association, of topical and systemic steroids and NSAIDs, in order to take advantage of their not proven, but evidence-based synergistic effect sometimes combined with the anti-inflammatory action of mydriatics. 20,2325  
Nonsteroidal anti-inflammatory drugs are widely used agents, which despite their chemical heterogeneity, share similar therapeutic properties and adverse effects. 3136  
Nonsteroidal anti-inflammatory drugs are cyclo-oxygenase (COX1-COX2), pro-inflammatory prostaglandins (PGs), and tromboxanes potent inhibitors. 18,19 In the current ophthalmologic practice, they are mainly used to maintain pupil dilation during intraocular surgery, 31 to give relief to ocular allergic diseases symptoms, 3133 to reduce discomfort after refractive surgery, 34 to treat postoperative pain and/or inflammation, and to prevent postsurgical CME. 35,36 For decades, their therapeutic efficacy for these conditions has been well established. New ongoing studies are trying to detect their efficacy in the anti-inflammatory treatment of diabetic retinopathy and AMD, which are actually recognized conditions related to the pathogenic role of pro-inflammatory PGs. 3537 Topical NSAIDs are the lowest risk alternative therapy to steroids; they avoid side effects related to prolonged topical administration of steroids, including glaucoma, cataract, increased infection susceptibility, and delayed wound healing. 3843 Furthermore, though studies comparing NSAIDs with corticosteroids showed no significant difference between results of these treatments, NSAIDs treatment appears to be more effective than topical steroids in re-establishing the blood–aqueous barrier, as quantitatively measured with anterior ocular fluorophotometry. 39,40 Our experience showed that NSAIDs are an intermediate treatment step to these conditions. 
In the last few decades, double-masked, randomized, active, and placebo-controlled studies, including patients undergoing cataract surgery, have reported anti-inflammatory effects from topically applied 0.1% INDOM, 0.03% flurbiprofen, 0.5% ketorolac, and 0.1% diclofenac ophthalmic preparations. The correlations between slit-lamp observations and anterior ocular fluorophotometry or laser cell flare meter methodology are consistent on their efficacy (Rho DS, et al. IOVS 2006;47:ARVO E-Abstract 5211). 4448  
A number of studies have established the safety and efficacy of 0.1% INDOM in the treatment of postoperative inflammation and pain and in the prevention and treatment of CME, 4651 but no studies are available on the more concentrated 0.5% INDOM eye drops, which seem to be more effective in relationship with a higher concentration rate in the vitreous and in the retina, though without any improvement in side-effects. 
Related to the availability of 0.5% INDOM single-dose eye drops in our country, and following a recent published work of Bucolo and coworkers, 52 we decided to study and compare efficacy and tolerance of this drug versus a placebo formulation (vehicle of the drops) for the treatment of uveitic ME Bucolo evaluated the ocular pharmacokinetics of two different INDOM formulations (0.1% and 0.5%, respectively), in rabbit eyes and the conclusions were that 0.5% INDOM eye drops showed better ocular distribution and relevant drug concentration levels in the posterior pole of the eye, useful to manage retinal inflammatory conditions, when compared with 0.1% concentrations. 
Indomethacin eye drops are more soluble and penetrating into eye tissues when they are complexated with cyclodextrins or formulated in ophthalmic suspension and added to artificial tears, 33,37,39 such as hydroxy-propyl-methil-cellulose (which is also present in the formulation we used), thus preserving corneal epithelium integrity. 
Some works report that after topical NSAID use, corneal complications like superficial punctate keratitis, corneal infiltrates, epithelial defects (which are also potential secondary risk factors in affected or predisposed dry-eye subjects) and corneal melting, may be detected, but they are mostly in relationship with preserved eye drops. 53,54  
Thanks to the characteristics of INDOM (preservative-free solution, tear substitute vehicle of 0.5% INDOM) we have not observed, despite high daily dosage (QID) and long-term treatment, any problem of corneal toxicity or corneal damage or melting as reported sometimes to other drugs (also in the new generation NSAIDs group) (Chu YR, et al. IOVS 2006;47;E-Abstract 74). 54 57  
We did not take into account the recently introduced NSAIDs bromfenac and nepafenac, because of, until the beginning of our study (November 2011), lack of studies on the retinal concentration of these drugs and their efficacy on the management of uveitic CME, besides the nonavailability of randomized studies and the emerging evidence of potential sight-threatening effects, such as corneal melting in predisposed subjects (Rho DS, et al. IOVS 2006;47:ARVO E-Abstract 5211). 4048  
In fact, after topical NSAID use, corneal complications are uncommon, but superficial punctate keratitis, corneal infiltrates, epithelial defects (which are also potential secondary risk factors in affected or predisposed dry-eye subjects), and corneal melting have been sometimes reported, mostly in relationship with preserved eye drops. 4954  
Concerning our study, we did not take into account the recently introduced NSAIDs bromfenac and nepafenac, because these formulations were available in the Italian market only some months before the beginning of our study (November 2011) and differently from INDOM eye drops, at this time, we had only some literature indications on their efficacy in the treatment of uveitic CME (Ogawa T, et al. IOVS 2006;47:ARVO E-Abstract 687). 58 71  
Recent works showed that bromfenac eye drops alone are ineffective for uveitic ME treatment, but may have a synergistic effect with intravitreal steroids in reducing CME in a follow-up period of more than 3 months of treatment. 68  
As Cable 69 presented, bromfenac 0.09% QID compared with nepafenac 0.1% three times a day after cataract surgery resulted in positive clinical outcomes of VA, macular volume, and retinal thickness. 
In contrast to aqueous drug levels, there is a paucity of human studies measuring NSAID levels in the vitreous after topical application. A single study measured vitreous drug levels in patients who received ketorolac 0.4% four times per day, bromfenac 0.09% twice a day, or nepafenac 0.1% three times a day for 3 days before vitrectomy surgery; only ketorolac resulted in significantly lower vitreous PGE2 levels compared with placebo. 64  
For some authors, steroids have to be used in combination with NSAIDs for CME treatment to obtain a synergistic effect. 4043 It is important to stress that in the 31 patients included in our study over the full period of follow-up, we never changed ongoing systemic steroid nor immunosuppressive biological treatment. 
Moreover, the patients were permitted only twice during the follow-up period, and only in the case of acute relapse of uveitis, to undertake a pulsed period of steroids (0.2% dexamethasone eye drops 3 times a day for 5 days then tapering to 2 weeks), and mydriatics (1% tropicamide eye drops once or twice a day for 10 days) while continuing 0.5% INDOM eye drops. 
Only 17 eyes (36.9%) needed this rescue treatment because of anterior acute uveitis relapses mainly related to HLA B27 positivity or autoimmune uveitis. 
Primary end points of more recent studies on uveitic CME take into account VA, degree of ME, and a combination of both. New tridimensional Spectralis OCT instruments can help in diagnosis by also showing the hidden forms of uveitis-related ME and provide quantitative and repeated appraisals of CFT. 1113,7274  
A work by Sivaprasad 49 showed that inner-retinal uveitic CME is more resistant to therapy than other patterns (diffuse or CME), so because of OCT we shall achieve more useful information on its prognosis and on the usefulness of treatment for it. 
A study of Markomichelakis and coworkers 75 detected three different OCT patterns of uveitic ME, including diffuse ME, CME, and exudative retinal detachment. Epiretinal membrane coexisted in a significant percentage of patients. 
We included in our study OCT-detected diffuse ME and CME and, after 6 months, CFT showed a significant decrease in treated patients by an average of 150 μm (P < 0.0001, 180 days versus baseline) compared with the placebo group in which no significant improvement of ME was seen (P = 1, 180 days versus baseline). In more than 50% of eyes in the placebo group, their OCT-detected ME worsened, as compared with less than 10% in the treated group. 
Secondary study endpoints were VA and subjective symptoms' (itching, burning, photophobia, and watering; 0–3 points score) improvement detection. 
Visual acuity showed a statistically significant improvement in the treated-eyes group (P < 0.0001, 180 days versus baseline) and significant time-treatment ratio in the treated group only (P < 0.0001); only in Group B (0.5% indomethacin-treated eyes) a significant correlation between retinal thickness decrease and VA increase (R = −0.35022, P = 0.0170) was found after 6 months. 
No significant difference in subjective symptoms was observed, no adverse event occurred, except an INDOM-treated group patient who complained about eye burning at instillation during the first treatment month. 
The epiretinal membrane was detected by OCT in 17 eyes (36.9%). Seven eyes showed vitreomacular traction (15.2%). 
Vision recovery thanks to INDOM treatment was observed in patients suffering from CME, but it was limited in subjects presenting an OCT-detected epiretinal traction membrane. 
Conclusions
Cystoid macular edema can result from the damage of the inner or the outer blood–ocular barrier and it is a well-known endpoint of various ocular diseases. It is one of the major causes of legal blindness in uveitis patients. Optical coherence tomography is a powerful method to assess the retinal thickness and how it changes throughout therapy. Clinical experience has shown that pseudophakic and acute uveitic CME usually respond well to local therapy with steroids and NSAIDs. 
Our study showed that a 6-month treatment of 0.5% INDOM eye drops was able to improve inflammatory acute ME related to uveitis in a statistically significant number of eyes compared with the placebo group. Those recalcitrant to treatment in our study were related to chronic forms or to the presence of a vitreomacular traction. 
Conclusions of our work are that it is important to treat cystoid inflammatory ME at a very early stage, before it becomes refractory to any treatment, and that 0.5% INDOM eye drops with tear-substitute vehicle are effective and devoid of any side effects in acute ME long-term treatment when ME presents without any epiretinal tractional membrane. 
Acknowledgments
A portion of this work has been published previously as an ARVO abstract: Zurria M, et al. IOVS 2013: ARVO E-Abstract 105. 
Disclosure: P. Allegri, None; U. Murialdo, None; S. Peri, None; R. Carniglia, None; M.G. Crivelli, None; S. Compiano, None; S. Autuori, None; A. Mastromarino, None; M. Zurria, None; Alfa Intes (F, E); G. Marrazzo, Alfa Intes (F, E) 
References
Okhravi N Lightman S. Cystoid macular edema in uveitis. Ocul Immunol Inflamm . 2003; 11: 29–38. [CrossRef] [PubMed]
de Smet MD Okada AA. Cystoid macular edema in uveitis. Dev Ophthalmol . 2010; 47: 136–147. [PubMed]
Rothova A. Inflammatory cystoid macular edema. Curr Opin Ophthalmol . 2007; 18: 487–492. [CrossRef] [PubMed]
Lardenoye CW van Kooij B Rothova A. Impact of macular edema on visual acuity in uveitis. Ophthalmology . 2006; 113: 1446–1449. [CrossRef] [PubMed]
Bringmann A, Reichenbach A, Wiedermann P. Pathomechanisms of cystoids macular edema. Ophthalmic Res . 2004; 36: 241–249. [CrossRef] [PubMed]
Guex-Crosier Y. The pathogenesis and clinical presentation of macular edema in inflammatory diseases. Doc Ophthalmol . 1999; 97: 297–309. [CrossRef] [PubMed]
Ursell PG Spalton DJ Whitcup SM Nussenblatt RB. Cystoid macular edema after phacoemulsification: relationship to blood-aqueous barrier damage and visual acuity. J Cataract Refract Surg . 1999; 25: 1492–1475. [CrossRef] [PubMed]
Johnson MW. Etiology and treatment of macular edema. Am J Ophthalmol . 2009; 147: 11–21. [CrossRef] [PubMed]
Saishin Y Takahashi K Melia M Vinores SA Campochiaro PA. Inhibition of protein kinase C decreases prostaglandin–induced breakdown of the blood-retinal barrier. J Cell Physiol . 2003; 195: 210–219. [CrossRef] [PubMed]
Leal EC Manivannan A Hosoya K. Inducible nitric oxide synthase isoform is a key mediator of leukostasis and blood-retinal barrier breakdown in diabetic retinopathy. Invest Ophthalmol Vis Sci . 2007; 48: 5257–5265. [CrossRef] [PubMed]
Tran TH de Smet MD Bodaghi B Fardeau C Cassoux N Lehoang P. Uveitic macular oedema: correlation between optical coherence tomography patterns with visual acuity and fluorescein angiography. Br J Ophthalmol . 2008; 92: 922–927. [CrossRef] [PubMed]
Hunter RS Skondra D Papaliodis G Sobrin L. Role of OCT in the diagnosis and management of macular edema from uveitis. Semin Ophthalmol . 2012; 27: 236–241. [CrossRef] [PubMed]
Iannetti L Spinucci G Abbouda A de Geronimo D Tortorella P Accorinti M. Spectral-domain optical coherence tomography in uveitic macular edema: morphological features and prognostic factors. Ophthalmologica . 2012; 228: 13–18. [CrossRef] [PubMed]
Gaynes BI Fiscella R. Topical nonsteroidal anti-inflammatory drugs for ophthalmic use: a safety review. Drug Saf . 2002; 25: 233–250. [CrossRef] [PubMed]
Guex-Crosier Y. Non-steroidal anti-inflammatory drugs and ocular inflammation. Klin Mon Augenheilkd . 2001; 218: 305–308. [CrossRef]
Warren KA Bahrani H Fox JE. Non-steroidal anti-inflammatory drugs in combination therapy for the treatment of chronic pseudophakic cystoid macular edema. Retina . 2010; 30: 260–266. [CrossRef] [PubMed]
Nichols J Snyder RW. Topical nonsteroidal anti-inflammatory agents in ophthalmology. Curr Opin Ophthalmol . 1998; 9: 40–44. [CrossRef] [PubMed]
Waterbury LD Silliman D Jolas T. Comparison of cyclooxygenase inhibitory activity and ocular anti-inflammatory effects of ketorolac tromethamine and bromfenac sodium. Curr Med Res Opin . 2006; 22: 1133–1140. [CrossRef] [PubMed]
Van Haeringen NJ van Sorge AA Carballosa Core-Bodelier VM. Constitutive cyclooxygenase-1 and induced cyclooxygenase-2 in isolated human iris inhibited by S(+) flurbiprofen. J Ocul Pharmacol Ther . 2000; 16: 353–361. [CrossRef] [PubMed]
Schilling H Pauleikhoff D Schrenk M Wessing A. Therapy of cystoid diffuse macular edema after uveitis and cataract surgery with carbonic anhydrase inhibitor acetazolamide. Klin Monbl Augenheilkd . 1993; 202: 206–211. [CrossRef] [PubMed]
Neri P Mariotti C Cimino L Mercanti L Giovannini A. Long term control of cystoid macular oedema in noninfectious uveitis with mycofenolate mofetil. Int Ophthalmol . 2009; 29: 127–133. [CrossRef] [PubMed]
Deuter CM Kötter I Günaydin I Stübiger N Doycheva DG Zierhut M. Efficacy and tolerability of interferon alpha treatment in patients with chronic cystoid macular oedema due to non-infectious uveitis. Br J Ophthalmol . 2009; 93: 906–913. [CrossRef] [PubMed]
Cho H Madu A. Etiology and treatment of the inflammatory causes of cystoid macular edema. J Inflamm Res . 2009; 2: 37–43. [CrossRef] [PubMed]
Karim R Sykakis E Lightman S Fraser-Bell S. Interventions for the treatment of uveitic macular edema: a systematic review and meta-analysis. Clin Ophthalmol . 2013; 7: 1109–1144. [CrossRef] [PubMed]
Multicenter Uveitis Steroid Treatment Trial Research Group, Kempen JH Altaweel MM Holbrook JT Jabs DA Sugar EA. The multicenter uveitis steroid treatment trial: rationale, design, baseline characteristics. Am J Ophthalmol . 2010; 149: 550–561. [CrossRef] [PubMed]
Becker M Davis J. Vitrectomy in the treatment of uveitis. Am J Ophthalmol . 2005; 140: 1096–1105. [CrossRef] [PubMed]
Gutfleisch M Spital G Mingels A Pauleikhoff D Lommatzsch A Heiligenhaus A. Pars plana vitrectomy with IVTA effect on uveitic cystoid macular oedema and treatment limitations. Br J Ophthalmol . 2007; 91: 345–348. [CrossRef] [PubMed]
Grover S Murthy RK Brar VS Chalam KV. Normative data for macular thickness by high-definition spectral-domain optical coherence tomography (spectralis). Am J Ophthalmol . 2009; 148: 266–271. [CrossRef] [PubMed]
Giani A Cigada M Choudhry N Reproducibility of retinal thickness measurements on normal and pathologic eyes by different optical coherence tomography instruments. Am J Ophthalmol . 2010; 150: 815–824. [CrossRef] [PubMed]
Wolf-Schnurrbusch UE Ceklic L Brinkmann CK Macular thickness measurements in healthy eyes using six different optical coherence tomography instruments. Invest Ophthalmol Vis Sci . 2009; 50: 3432–3437. [CrossRef] [PubMed]
Stewart R Grosserode R Cheetham JK Rosenthal A. Efficacy and safety profile of ketorolac 0.5% ophthalmic solution in the prevention of surgically induced miosis during cataract surgery. Clin Ther . 1999; 21: 723–732. [CrossRef] [PubMed]
Tinkelman DG Rupp G Kaufman H Pugely J Schulz N. Double masked, paired-comparison clinical study of ketorolac tromethamine 0.5% ophthalmic solution compared with placebo eyedrops in the treatment of seasonal allergic conjunctivitis. Surv Ophthalmol . 1993; 38: 133–140. [CrossRef] [PubMed]
Tauber J Raizman MB Ostrov CS A multicenter comparison of the ocular efficacy and safety of diclofenac 0.1% solution with that of ketorolac 0.5% solution in patients with acute seasonal allergic conjunctivitis. J Ocular Pharmacol Ther . 1998; 14: 137–145. [CrossRef]
Solomon KD Donnenfeld ED Raizman M Safety and efficacy of ketorolac tromethamine 0.4% ophthalmic solution in post-photorefractive keratectomy patients. J Cataract Refract Surg . 2004; 30: 1653–1660. [CrossRef] [PubMed]
O'Brien TP. Emerging guidelines for use of NSAID therapy to optimized cataract surgery patient care. Curr Med Res Opin . 2005; 21: 1131–1137. [CrossRef] [PubMed]
McColgin AZ Heier JS. Control of intraocular inflammation associated with cataract surgery. Curr Opin Ophthalmol . 2000; 1: 3–6. [CrossRef]
Wilkinson-Berka JL Alousis NS Kelly DJ Gilbert RE. COX-2 inhibition and retinal angiogenesis in a mouse model of retinopathy of prematurity. Invest Ophthalmol Vis Sci . 2003; 44: 974–979. [CrossRef] [PubMed]
Takahashi K Saishin Y Mori K Topical nepafenac inhibits ocular neovascularization. Invest Ophthalmol Vis Sci . 2003; 44: 409–415. [CrossRef] [PubMed]
Singh R Alpern L Jaffe GJ Evaluation of nepafenac in prevention of macular edema following cataract surgery in patients with diabetic retinopathy. Clin Ophthalmol . 2012; 6: 1259–1269. [CrossRef] [PubMed]
Simone JN Pendelton RA Jenkins JE. Comparison of the efficacy and safety of ketorolac tromethamine 0.5% and prednisolone acetate 1% after cataract surgery. J Cataract Refract Surg . 1999; 25: 699–704. [CrossRef] [PubMed]
Miyake K Masuda K Shirato S Comparison of diclofenac and fluorometholone in preventing cystoid macular edema after small incision cataract surgery: a multicenter prospective trial. Jpn J Ophthalmol . 2000; 44: 58–67. [CrossRef] [PubMed]
Frucht-Pery J Siganos CS Solomon A Topical indomethacin solution versus dexamethasone solution for treatment of inflamed pterygium and pinguecula: a prospective randomized clinical study. Am J Ophthalmol . 1999; 127: 148–152. [CrossRef] [PubMed]
Warren KA Fox JE. Topical nepafenac as an alternative treatment for cystoid macular edema in steroid responsive patients. Retina . 2008; 28: 1427–1434. [CrossRef] [PubMed]
Rossetti L Bujtar E Castoldi D Torrassa C Orzalesi N. Effectiveness of diclofenac eyedrops in reducing inflammation and the incidence of cystoid macular edema after cataract surgery. J Caract Refract Surg . 1996; 2: 794–799. [CrossRef]
Warren KA Bahrani H Fox JE. NSAIDs in combination therapy for the treatment of chronic pseudophakic cystoids macular edema. Retina . 2010; 30: 260–266. [CrossRef] [PubMed]
Solomon LD. Efficacy of topical flurbiprofen and indomethacin in preventing pseudophakic cystoid macular edema. Flurbiprofen-CME Study Group I. J Cataract Refract Surg . 1995; 21: 73–81. [CrossRef] [PubMed]
Weber M Kodjian L Kruse FE Zagorski Z Allaire CM. Efficacy and safety of indomethacin 0.1% eye drops compared with ketorolac 0.5% eye drops in the management of ocular inflammation after cataract surgery. Acta Ophthalmol . 2013; 91: e15–e21. [CrossRef] [PubMed]
Sivaprasad S Bunce C Crosby N Nwaobi R. Non-steroidal anti-inflammatory agents for treating cystoid macular oedema following cataract surgery. Cochrane Database Syst Rev . 2012; 2: CD004239.
Yavas GF Oztürk F Küsbeci T. Preoperative topical indomethacin to prevent pseudophakic CME. J Cataract Refract Surg . 2007; 33: 804–807. [CrossRef] [PubMed]
Halim MA Mahmoud AA. Formulation of indomethacin eye drops via complexation with cyclodextrins. Curr Eye Res . 2011; 36: 208–216. [CrossRef] [PubMed]
Bucolo C Melilli B Piazza C Zurria M Drago F. Ocular pharmacokinetics profile of different indomethacin topical formulations. J Ocul Pharmacol Ther . 2011; 27: 571–576. [CrossRef] [PubMed]
Kaiser PK Pineda R II. A study of topical nonsteroidal anti-inflammatory drops and no pressure patching in the treatment of corneal abrasions. Ophthalmology . 1997; 104: 1353–1359. [CrossRef] [PubMed]
Di Pascuale MA Whitson JT Mootha VV. Corneal melting after use of nepafenac in a patient with chronic cystoid macular edema after cataract surgery. Eye Contact Lens . 2008; 34: 129–130. [CrossRef] [PubMed]
Isawi H Dhaliwal DK. Corneal melting and perforation in Stevens Johnson syndrome following topical bromfenac use. J Cataract Refract Surg . 2007; 33: 1644–1646. [CrossRef] [PubMed]
Asai T Nakagami T Mochizuki M Three cases of corneal melting after instillation of a new nonsteroidal anti-inflammatory drug. Cornea . 2006; 25: 224–227. [CrossRef] [PubMed]
Yamaguchi M Ueda K Isowaki Mucoadhesive properties of chitosan-coated ophthalmic lipid emulsion containing indomethacin in tear fluid. Biol Pharm Bull . 2009; 32: 1266–1271. [CrossRef] [PubMed]
Hariprasad SM Akduman L Clever JA Ober M Recchia FM Mieler WF. Treatment of cystoid macular edema with the new-generation NSAID nepafenac 0.1%. Clin Ophthalmol . 2009; 3: 147–154. [CrossRef] [PubMed]
Hariprasad SM Callanan D Gainey S He YG Warren K. Topical nepafenac 0.1% for treatment of chronic uveitic cystoid macular edema. Retin Cases Brief Rep . 2008; 2: 304–308. [CrossRef] [PubMed]
Wolf EJ Braunstein A Shih C Braunstein RE. Incidence of visual significant pseudophakic macular edema after uneventful phacoemulsification in patients treated with nepafenac. J Cataract Refract Surg . 2007; 33: 1546–1549. [CrossRef] [PubMed]
Walters T Raizman M Ernest P Gayton J Lehmann R. In vivo pharmacokinetics and in vitro pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac. J Cataract Refract Surg . 2007; 33: 1539–1545. [CrossRef] [PubMed]
Endo N Kato S Haruyama K Shoji M Kitano S. Efficacy of bromfenac sodium ophthalmic solution in preventing cystoid macular oedema after cataract surgery in patients with diabetes. Acta Ophthalmol . 2010; 88: 896–900. [CrossRef] [PubMed]
Miyanaga M Miyai T Nejima R Maruyama Y Miyata K Kato S. Effect of bromfenac ophthalmic solution on ocular inflammation following cataract surgery. Acta Ophthalmol . 2009; 87: 300–305. [CrossRef] [PubMed]
Heier JS Awh CC Busbee BG Vitreous nonsteroidal anti-inflammatory drug concentrations and prostaglandin E2 levels in vitrectomy patients treated with ketorolac 0.4%, bromfenac 0.09%, and nepafenac 0.1%. Retina . 2009; 29: 1310–1313. [CrossRef] [PubMed]
Lindstrom R Kim T. Ocular permeation and inhibition of retinal inflammation: an examination of data and expert opinion on the clinical utility of nepafenac. Curr Med Res Opin . 2006; 22: 1237. [CrossRef]
Kapin MA Yanni JM Brady MT Inflammation-mediated retinal edema in the rabbit is inhibited by topical nepafenac. Inflammation . 2003; 27: 281–291. [CrossRef] [PubMed]
Jones J Francis P. Ophthalmic utility of topical bromfenac, a twice-daily nonsteroidal anti-inflammatory agent. Expert Opin Pharmacother . 2009; 10: 2379–2385. [CrossRef] [PubMed]
Radwan AE Arcinue CA Yang P Artornsombudh P Abu Al-Fadl EM, Foster CS. Bromfenac alone or with single intravitreal injection of bevacizumab or triamcinolone acetonide for treatment of uveitic macular edema. Graefes Arch Clin Exp Ophthalmol . 2013; 251: 1801–1806. [CrossRef] [PubMed]
Cable M. Comparison of bromfenac 0.09% QD to nepafenac 0.1% TID after cataract surgery: pilot evaluation of visual acuity, macular volume, and retinal thickness at a single site. Clin Ophthalmol . 2012; 6: 997–1004. [CrossRef] [PubMed]
Flach AJ. Topical nonsteroidal anti-inflammatory drugs in ophthalmology. Int Ophthalmol Clin . 2002; 42: 1–11. [CrossRef] [PubMed]
Kim SJ Doherty TJ Cherney EF. Intravitreal ketorolac for chronic uveitis and macular edema: a pilot study. Arch Ophthalmol . 2012; 130: 742–748. [CrossRef] [PubMed]
Wright PL Wilkinson CP Balyeat HD Popham J Reinke M. Angiographic cystoid macular edema after posterior chamber lens implantation. Arch Ophthalmol . 1988; 106: 740–744. [CrossRef] [PubMed]
Roesel M Henschel A Heinz C Dietzel M Spital G Heiligenhaus A. Fundus autofluorescence and spectral domain optical coherence tomography in uveitic macular edema. Graefes Arch Clin Exp Ophthalmol . 2009; 247: 1685–1689. [CrossRef] [PubMed]
Ossewaarde-van Norel J Camfferman LP Rothova A. Discrepancies between fluorescein angiography and optical coherence tomography in macular edema in uveitis. Am J Ophthalmol . 2012; 154: 233–239. [CrossRef] [PubMed]
Markomichelakis NN Halkiadakis I Pantelia E Patterns of macular edema in patients with uveitis: qualitative and quantitative assessment using optical coherence tomography. Ophthalmology . 2004; 111: 946–953. [CrossRef] [PubMed]
Figure 1
 
(A) Optical coherence tomography analysis from two representative patients from group A and B before and after treatment. (B) Central foveal thickness recorded in group A and group B during the follow-up period. **P < 0.001 versus baseline; §P < 0.0001 versus Group A at 180 days after treatment.
Figure 1
 
(A) Optical coherence tomography analysis from two representative patients from group A and B before and after treatment. (B) Central foveal thickness recorded in group A and group B during the follow-up period. **P < 0.001 versus baseline; §P < 0.0001 versus Group A at 180 days after treatment.
Figure 2
 
Visual acuity in decimal scale. **P < 0.001; ***P < 0.0001 versus baseline, no significant differences have been observed in group A patients.
Figure 2
 
Visual acuity in decimal scale. **P < 0.001; ***P < 0.0001 versus baseline, no significant differences have been observed in group A patients.
Table 1
 
Demographic and Clinical Characteristics
Table 1
 
Demographic and Clinical Characteristics
Group A, n = 16 (23 Eyes) Group B, n = 15 (23 Eyes) P Value
Age, y 59 ± 19.03 65.69 ± 11.27 0.10
Sex, male/female 6/9 5/11 0.61
Central foveal thickness at baseline, μm 390.6 ± 162.3 446.0 ± 149.4 0.11
Global discomfort index at baseline 1.08 ± 0.90 1.04 ± 0.7 0.81
Table 2
 
Main Causes of Inflammatory Macular Edema
Table 2
 
Main Causes of Inflammatory Macular Edema
Type of Uveitic CME Eyes N (%) Patients N (%)
Intermediate uveitis 23 (50) 15 (48.4)
Retinal vasculitis 17 (37) 10 (32)
Postinfective uveitis 3 (6.5) 3 (9.8)
HLA B27/anterior uveitis 3 (6.5) 3 (9.8)
Total 46 (100) 31 (100)
Table 3
 
Age Categorized by Quartiles
Table 3
 
Age Categorized by Quartiles
Min First Quartile (Q1) Median (Q2) Third Quartile (Q3) Max
Group (A+B) 22 53 62.35 ± 15.83 75 83
Group A 22 38 59 ± 19.03 75 83
Group B 38 60 65.7 ± 11.27 75 80
Table 4
 
Average Values of the Subjective Symptoms During the Time Course of the Treatment (Score: 0–3)
Table 4
 
Average Values of the Subjective Symptoms During the Time Course of the Treatment (Score: 0–3)
Baseline 30 d 90 d 180 d
Tearing
 Group A 0.7391 0.5217 0.3913 0.1304
 Group B 0.7391 0.6522 0.3478 0.1739
Burning sensation
 Group A 0.6522 0.3913 0.1304 0.1304
 Group B 0.8261 0.5652 0.3478 0.2609
Photophobia
 Group A 0.6957 0.5652 0.3478 0.1304
 Group B 0.6522 0.5652 0.4348 0.1739
Itching
 Group A 0.8261 0.4348 0.2174 0.1304
 Group B 0.7391 0.7826 0.4783 0.3043
Global discomfort index
 Group A 1.0870 0.4348 0.2174 0.1304
 Group B 1.0435 0.7826 0.6087 0.3478
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