• Users Online: 51558
  • Home
  • Print this page
  • Email this page

   Table of Contents      
ORIGINAL ARTICLE
Year : 2019  |  Volume : 67  |  Issue : 5  |  Page : 594-598

Comparison of the safety and efficacy of topical Tacrolimus (0.03%) versus dexamethasone (0.05%) for subepithelial infiltrates after adenoviral conjunctivitis


Department of Ophthalmology, Laser Eye Clinic, Noida, UP, India

Date of Submission30-Aug-2018
Date of Acceptance05-Jan-2019
Date of Web Publication22-Apr-2019

Correspondence Address:
Prof. Rahul Bhargava
B2-004, Ananda Apartments, Sector-48, Noida, UP - 201301
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijo.IJO_1352_18

Rights and Permissions
  Abstract 


Purpose: To compare the safety and efficacy of tacrolimus 0.03% ointment with dexamethasone 0.05% ointment for subepithelial infiltrates (SEIs) following adenoviral keratoconjunctivitis (AK). Methods: A randomized, double blind trial was done. Eligibility criteria was corrected distance visual acuity of 6/9 Snellen or worse for at least 4 weeks with corneal SEIs following AK. The grading of SEIs was done on a scale of 0 to 3; 0, no infiltrates, 1 mild infiltration, 2 moderate infiltration and 3, severe infiltration. Consecutive patients with SEIs following AK were randomized to receive either topical tacrolimus 0.03% or dexamethasone 0.05% ointment twice daily for 6 months. Treatment was successful if there was reduction of SEIs and improvement in vision. Results: A total of 45 patients each were assigned to the Tacro and Dexa groups, respectively. Baseline characteristics of patients did not differ significantly (P > 0.001). There was a significant change in symptoms, vision and SEIs in both the groups. However, the magnitude was greater in tacro group. Treatment was successful in 37 (92.5%) patients in Tacro and 34 (85%) patients in dexa group. In dexa group, after a period of 1.24 ± 0.24 months, 7 (15.6%) patients developed a significant rise in intraocular pressure (IOP). Three (7.5%) eyes in tacro and 6 (15%) eyes in dexa group had recurrence of SEIs after cessation of therapy. Conclusion: Tacrolimus 0.03% is an effective alternative to dexamethasone 0.05% with low recurrence rate, no significant rise in IOP but may cause burning and foreign body sensation in some patients.

Keywords: Adenoviral keratoconjunctivitis, dexamethasone, subepithelial infiltrates, tacrolimus


How to cite this article:
Bhargava R, Kumar P. Comparison of the safety and efficacy of topical Tacrolimus (0.03%) versus dexamethasone (0.05%) for subepithelial infiltrates after adenoviral conjunctivitis. Indian J Ophthalmol 2019;67:594-8

How to cite this URL:
Bhargava R, Kumar P. Comparison of the safety and efficacy of topical Tacrolimus (0.03%) versus dexamethasone (0.05%) for subepithelial infiltrates after adenoviral conjunctivitis. Indian J Ophthalmol [serial online] 2019 [cited 2024 Mar 28];67:594-8. Available from: https://journals.lww.com/ijo/pages/default.aspx/text.asp?2019/67/5/594/256663



Adenoviral keratoconjunctivitis (AK) usually occurs as epidemics; serotypes 8 and 19 cause most outbreaks. Infection is usually transmitted through fomites or contaminated body fluids. The virus has been demonstrated in tears for up to 3 weeks after infection.[1] The cornea is usually involved 2 or 3 days after the onset of symptoms and most common presentation is multifocal subepithelial infiltrates (SEIs), which are considered pathognomonic of adenoviral infection.[2] In subcontinent countries, SEIs may be observed in about 50% of AK cases. These focal lesions may represent a cellular immune reaction against viral antigens deposited in the corneal stroma under the Bowman membrane.[3] Histopathologically, SEIs show disruption of collagen in the Bowman layer along with infiltration of lymphocytes, histiocytes, and fibroblasts; these are usually bilateral and often asymmetric and have the potential to cause significant ocular morbidity, reduced vision, photophobia, glare, halos, and foreign body sensation and can persist for months or years after the initial infection.[4],[5]

Although, AK is a self-limiting disease, most affected individuals seek treatment due to diminution of vision from persistent SEIs, pseudomembranes and iridocyclitis.[6],[7] Various modalities have been tried as treatment options for AK including palliative therapy, such as cool compresses, artificial tears, and topical steroids; it is believed that steroids, by suppressing conjunctival and corneal inflammation, provide symptomatic relief, but they do not shorten the course of the disease. The use of long-term topical steroids may be associated with side effects such as cataract and glaucoma, and topical administration of corticosteroids may also cause prolonged viral seeding.[8]

Tacrolimus exerts potent immunosuppressive and anti-inflammatory effects through the inhibition of T-cell activation; it suppresses the immune system and the inflammation by inhibiting an enzyme (calcineurin) crucial for the multiplication of T-cells.[9]

Topical application of tacrolimus (0.03%) has been found to be effective in treating giant papillary conjunctivitis and vernal keratoconjunctivitis.[10],[11] However, it's safety profile in ophthalmic applications need to be evaluated further. The present study evaluated the safety and efficacy of tacrolimus (0.03%) and dexamethasone phosphate (0.05%) ointment in patients with SEIs following AK.


  Methods Top


Trial population

Across 3 referral eye centers in the subcontinent, 126 patients were diagnosed with AK from January 2015 through September 2017. Out of these, 110 (87.3%) met none of the exclusion criteria and were asked to attend an eligibility-confirmation visit approximately 5 days later. During this period, these patients were provided with a run-in antibiotic ointment. Of the 102 patients who returned for the eligibility confirmation visit, 96 (94.1%) were eligible for inclusion in the trial. The institutional review boards and the local ethics committee approved the trial. Written informed consent was obtained from all patients willing to participate in the study based on the tenets of the declaration of Helsinki.

Eligibility criteria

Eligibility criteria were an age of 18 years or older and diminution of vision (corrected distance visual acuity of 6/9 Snellen or worse) for at least 4 weeks with SEIs following AK. SEIs were graded on a scale of 0 to 3 by an independent investigator who was not a study surgeon on slit-lamp biomicroscopic examination (depending on depth of stromal infiltration, [Figure 1]); 0, no infiltrates, 1 mild infiltration, 2 moderate infiltration and 3, severe infiltration. [Figure 2]a depicts moderate stromal in infiltration following AK. Patient's symptoms were evaluated by a non-validated questionnaire (Dry Eye Scoring System, DESS). The minimum score for inclusion was 1 (i.e. any symptomatic patient). A score of 0-3 was assigned to common symptoms like blurring of vision, itching or burning, sandy or gritty sensation, and redness, respectively (DESS©). When symptoms are absent, the score was (0), sometimes present (1), frequently present (2), and always present (3). A score of 0-6 was mild, 6.1- 12 moderates, and 12.1-18 severely symptomatic patient.[12]
Figure 1: Moderate stromal infiltration (Grade 2) in a patient following adenoviral conjunctivitis

Click here to view
Figure 2: Corneal sub-epithelial infiltrates involving the visual axis (a)before and (b) following intervention

Click here to view


Exclusion criteria

Patients who received any topical or systemic medications, had ocular disease like uveitis, glaucoma, or active keratitis, used corticosteroid eye drops; and those who had any ocular operations were excluded from the study.

Randomization, masking, and sample size calculation

To calculate the sample size and to compare the mean difference in SEI scores between the 2 groups, a pilot study was first done on 10 subjects. The mean decrease in SEI score in the tacrolimus group was 1.8 and, in the dexamethasone, group was 1.5, respectively. The common SD was 0.4. Assuming 1:1 randomization, 90% power (alpha = 0.05), and a precision error of 5% to detect difference of 20% or more in SEI score between 2 groups, the estimated sample size in each group was calculated to be 38 (https://www.stat.ubc.ca/~rollin/stats/ssize/n1.html).

Trial groups

Consecutive patients with SEI were randomly allocated to 1 of the 2 groups by a parallel assignment (1:1). The allocation codes were generated by a web-based module and was stratified according to clinical center with a permuted block method with randomly chosen block sizes. The generated codes were sealed in green envelopes and were opened by health care personnel not involved in patient care. The TACRO group received tacrolimus 0.03% ointment [TALIMUS-LS] twice daily and DEXA group received dexamethasone 0.05% ointment [ORBIDEX] twice daily for 6 months. The subjects were masked to the contents. The 2 types of ointments were like each other in appearance. The subjects were instructed to return the empty tubes on monthly visit, wherein 1 pack of ointment was provided to them. The regimen was reduced in frequency or suspended when the patient reported any symptoms or when a contraindication to treatment to any of active ointments developed. With resolution of symptoms or contraindications, the patient could restart or resume the regimen.

Outcome measures

The primary outcome measure was mean change in baseline in the SEI score. Changes in visual acuity and intraocular pressure (safety outcomes), and the incidence of adverse events were secondary outcome measures. Coordinators asked patients about adverse events during each visit (at 1, 3, and 6 months). Grading of SEIs and measurements of intraocular pressure (IOP) was performed by an independent investigator (AC) who was not a study surgeon; intraocular pressure was measured with non-contact tonometer (CT-60, Topcon Corporation, Japan) on each monthly visit (1, 2, 3, 4, 5 & 6 months). All patients, clinical staff, and laboratory personnel were unaware of the trial-group assignments.

Statistics

Statistical analysis was performed on an intent-to-treat basis using IBM, SPSS Statistics version 25 (IBM Inc.). One eye of each patient was selected at random for examination and subsequent evaluation. Independent t tests were performed to ensure group similarities at baseline; the assumptions of performing t tests were met. Chi-square tests were used for proportions. A one-way repeated-measures analysis of variance (ANOVA) was conducted to determine whether there were significant differences in mean test values over the course of 6 months of treatment. The values used for assessing change were the means of values obtained during the 3-month and 6-month visits; if a value from only one of these visits was available, that value was used. Comparisons of the mean change in continuous measures between trial groups and associated 95% confidence intervals were based on linear regression with a robust variance estimator. Differences between trial groups in the cumulative proportion of patients with an adverse event were evaluated with the log-rank test; Fisher's exact test was used when the number of patients in a group with a given adverse event was 3 or fewer.


  Results Top


Patients and adherence

A total of 45 patients were assigned to the Tacro group and 45 to the Dexa group. However, after excluding 5 patients in each group (adverse effects), 40 cases in each group were analyzed for results statistically. There were no significant imbalances between trial groups in baseline characteristics [Table 1]. The mean duration of follow up was slightly longer in Dexa group (9.4 ± 1.5 vs 9.9 ± 1.4, paired t-test, P = 0.010). There was a significant improvement (paired t-test, P < 0.001) in symptoms, visual acuity (converted to Log MAR units for comparison) and SEI scores in Tacro group [Table 2] and Dexa group [Table 3], respectively. The mean symptom score decreased significantly by approximately 3 points in each group, during follow up, with greater improvement by 0.4 points in tacro group (95% CI, 2.7 to 3.8, P = 0.001). The mean Log MAR CDVA decreased by 0.22 points in each group with a greater change by 0.18 points in tacro group (95% CI, 0.22 to 0.27, P < 0.001). The mean SEI score decreased by 3 points in Tacro group and 1.5 points in dexa group, with a greater improvement by 1.5 points in tacro group (95% CI, 1.96-2.14, P = 0.001). In tacro group, 34 (85%) patients had complete resolution of symptoms at final follow up examination [Figure 2]b as compared to 30 (75%) in dexa group, respectively. [Figure 3] depicts the change in symptom score, vision, SEI Score and intraocular pressure in the two groups.
Figure 3: Subepithelial infiltrates (SEIs) were graded on a scale of 0 to 3 with higher scores indicating greater involvement. Subjective symptoms were graded on a score of 0-18 with higher scores indication sever symptoms.[12] In each trial group, there was a significant change between baseline and 6 months (with time as a continuous variable) in symptoms, vision and SEI score (P < 0.001 for change for each measure in each group). In dexa group, there was a significant increase in intraocular pressure

Click here to view
Table 1: Baseline characteristics of patients

Click here to view
Table 2: Mean test values in tacro group

Click here to view
Table 3: Mean test values in dexa group

Click here to view


Adverse effects

In tacro group, 8 (17.8%) patients could not tolerate the medication due to burning, redness and foreign body sensation in eyes. The dose of medication was reduced to once daily at bedtime. However, 5 (11.1%) patients declined to continue the medication beyond one month due to persistent ocular symptoms and were excluded from the study; the treatment was successful in the remaining three patients who could continue with twice daily medication at three months.

In dexa group, after a period of 1.24 ± 0.24 months, 7 (15.6%) patients developed rise in intraocular pressure (IOP) after topical medication [Figure 3]. These patients were referred to glaucoma clinic for control of IOP. Out of these 5 (11.1%) patients had sustained rise in IOP and were advised to discontinue further treatment with dexamethasone. These patients were subsequently put on treatment with tacrolimus and tolerated the therapy well but were excluded from the study. In tacro group, no statistically significant changes in IOP values were observed when comparing the before-treatment means (mean, 15.8 ± 1.9; range, 12-19 mm Hg) to the measurement at the last follow-up (mean, 15.7 ± 1.8 6; range, 11--17 mm Hg) (paired t-test, P = 0.848).

Recurrence

Treatment was considered successful in 37 (92.5%) patients in Tacro group and 33 (82.5%) patients in dexa group with adequate control of SEIs during follow up [Figure 2]b. However, 3 (7.5%) eyes in tacro group and 7 (17.5%) eyes in dexa group had recurrence of SEIs after cessation of therapy. In recurrent cases in tacro group, tacrolimus (0.03%) was reintroduced in combination with topical steroids, which were tapered over a period of one month. Tacrolimus ointment was maintained for 6 months in 2 eyes and for one year in one eye without recurrence of SEIs after cessation of drug. In dexa group, dexamethasone 0.05% ointment was reintroduced, and 2 eyes were maintained for 6 months without recurrence of infiltrates. However, tapering was unsuccessful in 5 eyes on two attempts and were shifted to treatment with tacrolimus recently.


  Discussion Top


Corneal SEIs following AK are bothersome for patients as they may persist for months or years after initial infection, causing significant ocular morbidity.[13] Chronicity of the disease is often compounded by long term therapies due to lack of an effective antiviral agent against adenovirus.[14] In a clinical study, topical cidofovir, used alone or in combination with topical cyclosporine, did not accelerate improvement of clinical symptoms of acute adenoviral keratoconjunctivitis compared with the natural course of disease.[15] This shortcoming has led to the exploration and trial of other modalities of treatment.

The use of topical steroids to treat SEIs is controversial. They are frequently prescribed by eye care providers in acute phase, although this may only have a transient alleviating effect. The disease and infection durations could be prolonged because of increased adenovirus replication rate and extended viral shedding as demonstrated in animal model.[6] Second, steroids have the propensity to cause serious side effects like rise in IOP and development of cataract.

Topical 2% cyclosporine has been an alternative to treat subepithelial infiltrates in the acute phase of infection, but results, side effects and recurrence rates have been comparable to corticosteroids.[16]

This randomized, double masked trial compared the efficacy of 0.03% tacrolimus with 0.05% dexamethasone ointment for treating SEIs. The results suggest that there was a significant improvement (P < 0.001) in subjective symptoms, vision, and reduction in SEIs in both the treatment groups at 6 months. However, the magnitude of improvement in test parameters was higher in tacro group. Repeated measure ANOVA revealed that resolution of SEIs was quicker in tacro group (at three months of therapy) as compared to dexa group (after four months). Ghanem et al. applied 0.02% tacrolimus eye drops for the treatment of SEIs and observed a significant improvement in vision at final follow-up examination.[17] In the same way, Levinger et al. reported a significant improvement in the visual function of patients treated with 0.03% tacrolimus ointment after 18 weeks with a four-week wash-out period.[18]

The initial tolerability to the drug was significantly better in dexa group however, there was a significant rise in intraocular pressure; five (11.1%) out of 7 (15.6%) patients who had a sustained rise in IOP had to discontinue dexamethasone and shift to tacrolimus therapy. However, burning, redness and foreign body sensation were common with application of tacrolimus ointment and may be severe enough to discontinue treatment.

Subepithelial infiltrates have propensity to recur after cessation of therapy. Recurrence was more common (17.5%%) in dexa group and tapering of dose was unsuccessful after reintroduction of drug. In a study comparing topical loteprednol versus topical dexamethasone for treating SEIs after viral conjunctivitis, Kocluk et al. found that both groups were had substantial recurrence and the difference between groups (Loteprednol versus dexamethasone) was not significant.[19]

The recurrence rate for tacrolimus (7.5%) observed in the present study were lower than other studies. Better patient compliance, patient counselling and reduction in dose (once daily) instead of complete withdrawal of drug could probably account for lower recurrence rates. Prado et al. observed a recurrence rate of 18.8% for tacrolimus compounded in pharmacy.[20] The recurrence rate may be significantly high (12.5%) for topical cyclosporine 0.05% therapy.[21]


  Conclusion Top


In conclusion, tacrolimus 0.03% ointment is more effective than dexamethasone 0.05% with low recurrence rate, no significant rise in IOP but may cause burning and foreign body sensation in some patients.

Acknowledgements

We are thankful to www.indianmedicalstats.com for statistical analysis in this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Zhang L, Zhao N, Sha J, Wang C, Jin X, Amer S, et al. Virology, and epidemiology analyses of global adenovirus-associated conjunctivitis outbreaks, 1953-2013. Epidemiol Infect 2016;144:1661-72.  Back to cited text no. 1
    
2.
Jhanji V, Chan TC, Li EY, Agarwal K, Vajpayee RB. Adenoviral keratoconjunctivitis. Surv Ophthalmol 2015;60:435-43.  Back to cited text no. 2
    
3.
Jones BR. The clinical features of viral keratitis and a concept of their pathogenesis. Proc R Soc Med 1958;51:917-24.  Back to cited text no. 3
    
4.
Chintakuntlawar AV, Zhou X, Rajaiya J, Chodosh J. Viral capsid is a pathogen-associated molecular pattern in adenovirus keratitis. PLoS Pathog 2010;6:e1000841.   Back to cited text no. 4
    
5.
Adhikary AK, Banik U. Human adenovirus type 8: The major agent of epidemic keratoconjunctivitis (EKC). J Clin Virol 2014;61:477-86.  Back to cited text no. 5
    
6.
Romanowski EG, Yates KA, Gordon YJ. Topical corticosteroids of limited potency promote adenovirus replication in the Ad5/NZW rabbit ocular model. Cornea 2002;21:289-91.  Back to cited text no. 6
    
7.
Asena L, Şıngar Özdemir E, Burcu A, Ercan E, Çolak M, Altınörs DD. Comparison of clinical outcome with different treatment regimens in acute adenoviral keratoconjunctivitis. Eye (Lond) 2017;31:781-7.  Back to cited text no. 7
    
8.
Romanowski EG, Yates KA, Gordon YJ. Short-term treatment with a potent topical corticosteroid of an acute ocular adenoviral infection in the New Zealand white rabbit. Cornea 2001;20:657-60.  Back to cited text no. 8
    
9.
Levinger E, Slomovic A, Sansanayudh W, Bahar I, Slomovic AR. Topical treatment with 1% cyclosporine for sub epithelial infiltrates secondary to adenoviral keratoconjunctivitis. Cornea 2010;29:638-40.  Back to cited text no. 9
    
10.
Kymionis GD, Goldman D, Ide T, Yoo SH. Tacrolimus ointment 0.03% in the eye for treatment of giant papillary conjunctivitis. Cornea 2008;27:228-9.  Back to cited text no. 10
    
11.
Joseph MA, Kaufman HE, Insler M. Topical tacrolimus ointment for treatment of refractory anterior segment inflammatory disorders. Cornea 2005;24:417-20.  Back to cited text no. 11
    
12.
Bhargava R, Kumar P. Oral omega-3 fatty acid treatment for dry eye in contact lens wearers. Cornea 2015;34:413-20.  Back to cited text no. 12
    
13.
Garcia-Zalisnak D, Rapuano C, Sheppard JD, Davis AR. Adenovirus ocular infections prevalence, pathology, pitfalls, and practical pointers. Eye Contact Lens 2018;44(Suppl 1):S1-7.  Back to cited text no. 13
    
14.
Lenaerts L, Naesens L. Antiviral therapy for adenovirus infections. Antiviral Res 2006;71:172-80.  Back to cited text no. 14
    
15.
Hillenkamp J, Reinhard T, Ross RS, Böhringer D, Cartsburg O, Roggendorf M, et al. Topical treatment of acute adenoviral keratoconjunctivitis with 0.2% cidofovir and 1% cyclosporine: A controlled clinical pilot study. Arch Ophthalmol 2001;119:1487-91.  Back to cited text no. 15
    
16.
Muftuoglu IK, Akova YA, Gungor SG. Effect of 0.05% topical cyclosporine for the treatment of symptomatic subepithelial infiltrates due to adenoviral keratoconjunctivitis. Int J Ophthalmol 2016;9:634-5.  Back to cited text no. 16
    
17.
Ghanem RC, Vargas JF, Ghanem VC. Tacrolimus for the treatment of subepithelial infiltrates resistant to topical steroids after adenoviral keratoconjunctivitis. Cornea 2014;33:1210-3.  Back to cited text no. 17
    
18.
Levinger E, Trivizki O, Shachar Y, Levinger S, Verssano D. Topical 0.03% tacrolimus for subepithelial infiltrates secondary to adenoviral keratoconjunctivitis. Graefes Arch Clin Exp Ophthalmol 2014;252:811-6.  Back to cited text no. 18
    
19.
Koçluk Y, Sukgen EA, Cevher S, Mat E. Symptomatic treatment of subepithelial infiltrates after viral conjunctivitis: Loteprednol or dexamethasone? Ocul Immunol Inflamm 2017;25:649-53.  Back to cited text no. 19
    
20.
Berisa Prado S, Riestra Ayora AC, Lisa Fernández C, Chacón Rodríguez M, Merayo-Lloves J, Alfonso Sánchez JF. Topical tacrolimus for corneal subepithelial infiltrates secondary to adenoviral keratoconjunctivitis. Cornea 2017;36:1102-5.  Back to cited text no. 20
    
21.
Okumus S, Coskun E, Tatar MG, Kaydu E, Yayuspayi R, Comez A, et al. Cyclosporine a 0.05% eye drops for the treatment of subepithelial infiltrates after epidemic keratoconjunctivitis. BMC Ophthalmol 2012;12:42.  Back to cited text no. 21
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]


This article has been cited by
1 Topical interferon alpha-2b is a proper alternative for management of adenoviral keratitis: A case report
Mitra Akbari
Journal of Advanced Pharmacy Education and Research. 2023; 13(2): 12
[Pubmed] | [DOI]
2 Topical pharmacologic interventions versus placebo for epidemic keratoconjunctivitis
Su-Hsun Liu, Barbara S Hawkins, Sueko M Ng, Mark Ren, Louis Leslie, Genie Han, Irene C Kuo
Cochrane Database of Systematic Reviews. 2022; 2022(3)
[Pubmed] | [DOI]
3 Efficacy and Safety of Ophthalmic Preparations of Glucocorticoids in Patients with Epidemic Keratoconjunctivitis: A Systematic Review and Meta-analysis
Pengpeng Liu, Guangyao Li, Mei Han, Xiao Cheng, Ying Cui, MD, Qinglin Yang, MD, Chao Zhang
Therapeutic Innovation & Regulatory Science. 2022;
[Pubmed] | [DOI]
4 Topical Pharmacologic Interventions Versus Active Control, Placebo, or No Treatment for Epidemic Keratoconjunctivitis: Findings From a Cochrane Systematic Review
Su-Hsun Liu, Barbara S. Hawkins, Mark Ren, Sueko M. Ng, Louis Leslie, Genie Han, Irene C. Kuo
American Journal of Ophthalmology. 2022; 240: 265
[Pubmed] | [DOI]
5 Sequelae of microsporidial keratoconjunctivitis and its management
Amrita Mohanty, Sanchita Mitra, Aparajita Mallick, ManasRanjan Barik, Sujata Das, Smrutirekha Priyadarshini, SrikantK Sahu
Indian Journal of Ophthalmology. 2021; 69(6): 1537
[Pubmed] | [DOI]
6 Use of topical tacrolimus in ophthalmology: Nonsystematic review
MorganaArima Vedovato, ThaynaraQueiroz Mendes Do Carmo, LiviaCristina Rios, ViniciusCidral Corrêa, FernandaRibeiro Oliveira, NelsonChamma Capelanes, BernardoKaplan Moscovici
The Pan-American Journal of Ophthalmology. 2020; 2(1): 36
[Pubmed] | [DOI]
7 The Treatment Models for Adenoviral Keratoconjunctivitis in the Childhood Population
Sinan Bekmez, Erdem Eris
Ocular Immunology and Inflammation. 2020; : 1
[Pubmed] | [DOI]
8 Blepharitis: A Review on Human Clinical Trials with Synthetic and Natural Remedies
Vyshma Kizhuppully Viswambaran, Anavadhya K. A, Gopika Chandrababu, Amritha Babu, Gayathri Rajeev, Swati Gupta
Biomedical and Pharmacology Journal. 2020; 13(4): 1939
[Pubmed] | [DOI]
9

Management of Adenoviral Keratoconjunctivitis: Challenges and Solutions

Bisant A Labib, Bhawanjot K Minhas, DeGaulle I Chigbu
Clinical Ophthalmology. 2020; Volume 14: 837
[Pubmed] | [DOI]



 

Top
 
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
Abstract
Methods
Results
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed5741    
    Printed34    
    Emailed0    
    PDF Downloaded778    
    Comments [Add]    
    Cited by others 9    

Recommend this journal