Scale bar=100m. Lenglet S, Mach F, Montecucco F. Role of matrix metalloproteinase-8 in atherosclerosis. Drug information provided by: Merative, Micromedex. Quantitative real time PCR was performed to measure expression of inflammation cytokines and matrix metalloproteinases (MMP) in whole cornea lysates. If we combine this information with your protected Scale bar=1000 m. TIMP-1 binds MMP-9, while TIMP-2 binds MMP-2 and MMP-14. Immunofluorescent staining was performed in frozen tissue sections with rabbit polyclonal antibody anti-MMP-1 (1:50, NBP1-77209; Novus Biologicals), anti-MMP-9 (1:100; Santa Cruz Biotechnology, Dallas, TX), anti-IL-1 (1:100, Upstate-Millipore Corp., Bedford, MA), anti-neutrophil-gelatinase associated lipocalin (1:50, ab63929, Abcam, Cambridge, MA), goat anti-MMP-13 and goat anti-integrin 4 (1:100 dilution, sc-123630; 1:50 dilution, sc-6628, respectively, Santa Cruz Biotechnology, Dallas, TX, USA). UT=untreated cornea, BSS=corneas subjected to alkali burn and dry eye and treated topically with balanced salt solution, Dex=corneas subjected to alkali burn and dry eye and treated topically with dexamethasone, Doxy=corneas subjected to alkali burn and dry eye and treated topically with doxycycline, D=days, NGAL=Neutrophil-gelatinase associated lipocalin, NC=negative control. 7. Sinusitis is inflammation of the paranasal sinuses due to viral, bacterial, or fungal infections or allergic reactions. The hypoxanthine guanine phosphoribosyl transferase (HPRT-1) gene was used as an endogenous reference for each reaction to correct for differences in the amount of total RNA added. Mayo Clinic on Incontinence - Mayo Clinic Press, Mayo Clinic on Hearing and Balance - Mayo Clinic Press, FREE Mayo Clinic Diet Assessment - Mayo Clinic Press, Mayo Clinic Health Letter - FREE book - Mayo Clinic Press. Low Dose Doxycycline in the Treatment of Corneal Burn Fini ME, Cui TY, Mouldovan A, et al. Yoeruek E, Ziemssen F, Henke-Fahle S, et al. A total of six mice per experimental group at 2 and 5 days post-injury were euthanized. Reviglio VE, Rana TS, Li QJ, Ashraf MF, et al. Clinical and histopathological outcomes of subconjunctival triamcinolone injection for the treatment of acute ocular alkali burn in rabbits. However, its role in mature blood vessels is still not well understood. Intraocular corticosteroids best for treating complications of chronic Doxy had a moderate effect decreasing NGAL-MMP-9 complex (Figure 3C). sharing sensitive information, make sure youre on a federal Unable to load your collection due to an error, Unable to load your delegates due to an error. No perforations were observed in the Dex-treated corneas. A recent international Dry Eye Workshop (DEWS) defined dry eye as a "multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface which is accompanied by increased osmolarity of the tear film and inflammation of the ocular . Cholera Chlamydia Infection Epididymitis - Sexually Transmitted Gonococcal Infection - Uncomplicated Granuloma Inguinale Lymphogranuloma Venereum Nongonococcal Urethritis Malaria Prophylaxis Malaria Mice were topically treated either with Dex (0.1%), Dox (0.025%) or vehicle QID and observed daily for appearance of corneal perforation. Doxycycline protected the cornea from alkali burn injury by reducing TGF- 1, MMP-9, NF- B, and -SMA expression. It works by killing bacteria or preventing their growth. Results are presented as mean SEM milliunits. The gels were soaked in 0.25% Triton X-100 for 30 minutes at room temperature, and incubated in a digestion buffer containing 5 mmol/L phenylmethyl sulfonyl fluoride at 37C overnight. PMC 8600 Rockville Pike Here we subjected mice to unilateral alkali burn and concomitant desiccating stress and topically treated them with either Doxy or Dex and compared the effects to BSS-treated corneas (Figure 1A). All rights reserved. Scale bar=50m. Brown SI, Akiya S, Weller CA. Gelatinolytic activities appeared as clear bands of digested gelatin against a dark blue background of stained gelatin. Doxycycline is used to treat bacterial infections in many different parts of the body. Meibomitis: Causes, Treatment, Diagnosis, Prevention, and Pictures Doxycyclinea role in ocular surface repair - PMC The https:// ensures that you are connecting to the Li DQ, Chen Z, Song XJ, et al. Inflammatory. B. Doxycycline is used to treat infective diseases because of its broadspectrum efficacy. include protected health information. Al-Moujahed A, Chodosh J. Outcomes of an algorithmic approach to treating mild ocular alkali burns. Ibuprofen can relieve eye pain and inflammation. Some doctors may prescribe Minocycline, a different form of Tetracycline, with different risk factors. Increased neutrophil infiltration and myeloperoxidase activity was noted in the vehicle group compared to Dex 2 days post-injury. Our study showed that early initiation anti-inflammatory therapy is critical in controlling acute host response. Treatment of recalcitrant recurrent corneal erosions with inhibitors of matrix metalloproteinase-9, doxycycline and corticosteroids. We have not observed corneal perforations after alkali burns in mice unless these mice are subjected to a desiccating stress and cholinergic blockade.20 In our experiment with prolonged dosing of dexamethasone (up to 21 days), we did not observe any corneal perforations. Treatment with subantimicrobial dose doxycycline improves the efficacy of scaling and root planing in patients with adult periodontitis. official website and that any information you provide is encrypted Systemic tetracycline treatment of alkali-induced corneal ulceration in rabbits. Isotretinoin can also cause: Inflammation of the conjunctiva and eyelid (blepharoconjunctivitis) Light sensitivity (photophobia) Swelling of the optic nerve (papilledema) 4. Dex-treated corneas did not perforate even after continuous treatment for up to 21 days, indicating that prolonged therapy for up to 21 days does not promote corneal melting. Prevention by medroxyprogesterone of perforation in the alkali-burned rabbit cornea: inhibition of collagenolytic activity. Samtani S, Amaral J, Campos MM, et al. Diagnosis and Management of Red Eye in Primary Care | AAFP Kubben FJ, Sier CF, Hawinkels LJ, et al. Scale bar=1000 m. Bethesda, MD 20894, Web Policies Control mice were kept in a normal vivarium room (untreated animals, UT). A significant influx of Gr-1+ cells was observed in BSS-treated corneas 2 and 5 days post-injury; the infiltration was not restricted to the limbal area, but extended to the central cornea (Figure 4D). Corneal epithelial healing was assessed daily by instilling 1 L of 0.1% liquid sodium fluorescein onto the ocular surface. These findings demonstrate that early initiation of anti-inflammatory therapy is very efficacious in preserving corneal clarity and facilitating wound healing, while modulating MMP production and suppressing neutrophil infiltration. The immunoreactivity of corneas to collagenases (MMPs -1, -13) and MMP-9 was evaluated by immunostaining (Figure 3). Clipboard, Search History, and several other advanced features are temporarily unavailable. Effect of topical corticosteroids on ulceration in alkali-burned corneas. The application of metagenomic next-generation sequencing for. Doxycycline, Minocycline - NOT A DRY EYE Foundation It can also be used prevent malaria and treat infections caused by mites, ticks, or lice. Further research is needed to fully elucidate the potential of doxycycline as an anti-inflammatory agent, and the development of new topical vehicles could open ways to new therapeutic possibilities for dermatologists. Doxycycline: Do's and Don'ts - Review of Optometry Dex-treated corneas had the lowest corneal opacity scores. Our study showed that corneas treated with doxycycline healed faster than controls, had a smaller number of corneal perforations, decreased levels of MMP-9, MMP-13, TIMP-1, IL-1 and CXCL1 (at day 5) gene transcripts, decreased immunoreactivity of MMPs-1, -9 and 13 and levels of gelatinases in the cornea. It is characterised by facial flushing, erythema and telangiectasia, inflammatory papules, occasionally connective tissue hypertrophy and ocular involvement [1].The disease typically affects patients between the ages of 40 and 50, but ocular rosacea is more common between . You'll soon start receiving the latest Mayo Clinic health information you requested in your inbox. 1998-2023 Mayo Foundation for Medical Education and Research (MFMER). MMPs-1, -3, -8, -9,-13 and TIMP-1 transcripts peaked at 2 days and decreased by 5 days, while IL-6 continued to increase up to day 5 (Figure 2). Gutierrez-Fernandez A, Inada M, Balbin M, et al. Make your tax-deductible gift and be a part of the cutting-edge research and care that's changing medicine. Safety, penetration and efficacy of topically applied bevacizumab: evaluation of eyedrops in corneal neovascularization after chemical burn. Corneal epithelial defects were graded in digital images by two masked observers in a categorical manner (present/absent) to generate a survival curve. Reim M, Redbrake C, Schrage N. Chemical and thermal injuries of the eyes. Modulation of MMP-9 activity by NGAL. Mice with corneal perforations were not used any further studies. Quantitative real time PCR was performed using gene expression assay primers and MGB probes specific for murine targets described in Table 1. A unilateral alkali burn (AB) was created on the right cornea as described in materials and methods. Yoo SE, Lee DC, Chang MH. We observed an increase in NGAL immunoreactivity in the corneal epithelium of alkali-burned and dry eye. I have mentioned how my mentor at Harvard, Dr. Judah Folkman, used to comment that 20mg is the best for decreasing inflammation and that if he could put it in the water, he would. Inflammation in the eye can lead to fluid buildup in the central part of the eye's light-sensing retina, known as the macula, and decrease vision. Studies on a guinea pig model of corneal ulceration after ocular alkali burning. Biologic replicate samples were averaged. Total protein concentration was measured by the BCA protein assay as previously described.25. . Pal-Ghosh S, Pajoohesh-Ganji A, Tadvalkar G, Stepp MA. Eyes of all treatment groups were examined daily under a microscope (SMZ 1500, Nikon, Melville, New York) for presence of corneal perforation. Advertising revenue supports our not-for-profit mission. Bethesda, MD 20894, Web Policies This medication is also used to prevent malaria. Essential role for c-Jun N-terminal kinase 2 in corneal epithelial response to desiccating stress. This medication is known as a . Therapeutic strategies for ocular surface alkali injuries have been directed toward promoting epithelial healing and suppressing inflammation and tissue destruction, during the acute phase.1 Treatment of the chronic phases, including the anatomical sequelae, sometimes require a multidisciplinary approach and, very often, surgical procedures such as amniotic membrane, keratolimbal stem cell, or cornea transplantation.2 Although these approaches have slightly improved visual outcomes, visual outcomes from these injuries still poor, in large part due to inadequate control of inflammatory and proteolytic components of the wound healing response. Gierek M, Ochaa-Gierek G, Kitala D, abu W, Bergler-Czop B. Postepy Dermatol Alergol. Ocular rosacea - Diagnosis and treatment - Mayo Clinic Anti-inflammatory therapy decreases neutrophil infiltration. A wonderful patient did the research for me and found this article noting 20mg of Doxy does not affect the microbiome which is a key component to general health (see next blog post , https://drcremers.com/2018/11/is-doxycycline-20mg-better-for.html, https://drcremers.com/2018/05/doxycycline-and-neuropathy.html, https://drcremers.com/2014/11/low-dose-doxycycline-20mg-per-day.html. Relative fold expression of IL-1 and CXCL1 in whole corneas subjected to alkali burn and dry eye topically treated with BSS, Dex, or Doxy. Introduction Chemical injury of the eye is a common intractable ocular disease in the clinic. Sosne G, Szliter EA, Barrett R, et al. Gu Y, Walker C, Ryan ME, et al. Information is for End User's use only and may not be sold, redistributed or otherwise used for commercial purposes. To provide you with the most relevant and helpful information, and understand which recommended therapy is 2 g ceftriaxone delivered intravenously daily for 14 to 21 days or 200 mg of doxycycline taken orally twice a day for 10 to 20 days. While barely detected in nave corneas, increased immunoreactivity to NGAL was observed in the epithelium of BSS-treated corneas. Pro- and anti-inflammatory forms of interleukin-1 in the tear fluid and conjunctiva of patients with dry-eye disease. In addition, research in this field could help clarify pathogenic aspects of inflammatory dermatologic diseases responsive to this medication. P0.05 was considered statistical significant. Gordon MK, Desantis A, Deshmukh M, et al. There is a consensus that the prognosis of an alkali burn depends on the area of the insult, the penetration of the agent, and early treatment controlling host response and inflammation. Female C57BL/6 mice aged 68 weeks were purchased from Jackson Laboratories (Bar Harbor, ME, USA) and subjected to alkali burn associated with dry eye as previously described.20 Animals were euthanized after 2 or 5 days unless otherwise noted. In the majority of cases of chalazia, inflammatory conditions such as seborrheic dermatitis, acne rosacea, and chronic blepharitis are present. In addition, we investigated the expression of the cytokine IL-1 and the chemokine CXCL1 since they have been implicated in the migration of neutrophils.34,35 Dex treatment in the combined model significantly decreased the early peak of IL-1 and CXCL1 two days after initial injury, as well as at day 5. Doxycycline Attenuates Pig Intestinal Microbial Interactions and Changes Microbial Metabolic Pathways. Antiinflammatory therapy for dry eye - PubMed Doxycycline side effects Doxycycline oral tablet can cause side effects. privacy practices. Although not all of these side effects may occur, if they do occur they may need medical attention. A ny eye-care professional or patient will tell you that the treatment of dry eye has changed and evolved drastically over the years. Cyclosporin A is the first FDA approved therapy for this indication. Doxycycline works by inhibiting bacterial protein . Inclusion in an NLM database does not imply endorsement of, or agreement with, 2023 Jan 27;2023:7421325. doi: 10.1155/2023/7421325. The meibomian glands release meibum, the special oil that helps lubricate your eyes and. Oral antibiotics for chronic blepharitis - PMC - National Center for Due to its various mechanisms of action, doxycycline treats many medical and ocular pathology. 1. Two-way analysis of variance (ANOVA) with Bonferroni post hoc testing was used for statistical comparisons of gene expression. Dexamethasone greatly preserved corneal clarity, decreased neutrophil infiltration and expression of the neutrophil chemoattractant, CXCL1. Xiidra (topical lifitegrast 5%, Shire) is the first dry eye medication that targets integrin signaling as a lymphocyte function-associated antigen-1 (LFA-1) antagonist that blocks coupling of LFA-1 and ICAM-1. Kato T, Saika S, Ohnishi Y. Hidradenitis suppurativa: bacteriological study in surgical treatment. Doxycycline: Uses, Dosage, Side Effects, Warnings - Drugs.com AB was created at day 0 and animals were sacrificed after 2 or 5 days. Myeloperoxidase (MPO) activity was measured using a myeloperoxidase colorimetric activity assay kit as described by the manufacturer (Sigma-Aldrich, CA). Mayo Clinic does not endorse companies or products. Doxycycline Oral: Uses, Side Effects, Interactions, Pictures - WebMD Please enable it to take advantage of the complete set of features! Representative merged digital images of corneal cryosections immunostained for MMP-8 (in green) with propidium iodide nuclei counterstaining (red) in corneas subjected to the combined model topically treated with BSS, Dex or Doxy. Foster CS, Zelt RP, Mai-Phan T, Kenyon KR. Relative fold expression of IL-6, collagenases (MMPs -1, -8 and 13), the stromelysin MMP-3, the gelatinase MMP-9 and TIMP-1 in whole corneas subjected to a combined model of alkali burn and dry eye topically treated with BSS, Dex, or Doxy. C57BL/6 mice were subjected to the CM for 2 or 5 days (D). Preliminary studies with collagenase inhibitors. This site needs JavaScript to work properly. Alkali burns of the cornea are potentially sight-threatening, as alkali can penetrate rapidly into the eye and cause intense inflammation. Sinusitis - Ear, Nose, and Throat Disorders - Merck Manuals dark urine decreased appetite diarrhea diarrhea, watery and severe, which may also be bloody difficulty with swallowing dizziness fast heartbeat feeling of discomfort fever headache hives, itching, puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue hives or welts, itching, or rash increased thirst indigestion C. Representative gelatin zymogram showing MMP-9 and NGAL-MMP-9 bands in whole corneal lysates in the treatment groups. MMP-9 activity was evaluated by gelatin zymography, which showed increased amounts of both pro and active MMP-9 bands in the BSS group compared to control corneas (day 2 > day 5). Treatment of ocular rosacea: comparative study of topical cyclosporine Asterisks show significant p value compared to vehicle. Uses. Would you like email updates of new search results? Doxycycline-mediated inhibition of choroidal neovascularization. Last year, due to Lyme's disease (infection by Borrelia bacterium which is spread by ticks), her doctor prescribed doxycycline for 14 days. the unsubscribe link in the e-mail. Dexamethasone treatment paradoxically decreased TIMP-1, while doxycycline treatment did not. BSS- and Doxy-treated corneas subjected to the combined model showed corneal perforations as early as day 1 after the initial insult; however, more BSS than Dox-treated corneas perforated (27 vs. 14%, p=.03, Figure 1E). Doxycycline as an anti-inflammatory agent: updates in dermatology Check with your doctor immediately if any of the following side effects occur: Some side effects may occur that usually do not need medical attention. MPO activity has been used as a parameter of neutrophil infiltration.36 We measured MPO activity in corneal lysates in the treatment groups 2 days after injury. Chemical/thermal injuries to the eye are potentially blinding conditions. Lubricate your eyes. You may report side effects to the FDA at 1-800-FDA-1088. the contents by NLM or the National Institutes of Health. This content does not have an English version. This 125kDa band corresponds to the NGAL-MMP-9 complex.30,32 NGAL binds covalently to MMP-9 and this complex has been reported to protect MMP-9 from degradation and preserve MMP-9 activity in a concentration-dependent manner.30,33 Levels of serum NGAL-MMP-9 complex were increased in patients with active ulcerative colitis, correlated with neutrophil infiltration and it has been proposed as a surrogate marker of mucosal healing.51 NGAL immunoreactivity increased in the colonic epithelium in inflammatory and neoplastic, colorectal diseases.52 Increased levels of NGAL-MMP-9 have been reported in tears upon awakening53 and observed in tears of Sjgren syndrome patients.54 Therefore, the presence of NGAL-MMP-9 complex in BSS-treated corneas may indicate a mechanism to preserve MMP-9 activity. Yan L, Borregaard N, Kjeldsen L, Moses MA. Sizing Up Anti-inflammatories in Dry Eye Disease - Review of Optometry Before Click here for an email preview. Markoulli M, Papas E, Cole N, Holden BA. The localization of fluorescence indicates the sites of net gelatinolytic activity. official website and that any information you provide is encrypted Therapeutic strategies for ocular surface alkali injuries have been directed toward promoting epithelial healing and suppressing inflammation and tissue destruction, during the acute phase. Gordon GM, Austin JS, Sklar AL, et al. The site is secure. The contralateral eyes served as an untreated control (UT). This medication is used to treat a wide variety of bacterial infections, including those that cause acne. IL-17 disrupts corneal barrier following desiccating stress. How to take doxycycline Whenever oral antibiotics are taken, and particularly if they are taken long term, it is important to support gut health with good probiotics. Bright field digital images of alkali burn and dry eye combined model treated with either balanced salt solution (BSS), dexamethasone (Dex) or doxycycline (Doxy) 5 days (5D) post-injury. This algorithm included frequent use of topical corticosteroids, oral doxycycline, and oral vitamin C, along with amniotic membrane grafting if needed.61. This content does not have an English version. But, when it comes to prescribing oral antibiotics, we often hesitate or exhibit less confidence. Dry Eye: an Inflammatory Ocular Disease - PMC - National Center for health information, we will treat all of that information as protected health Once corneal perforation was observed, mice were euthanized. The tetracycline analogs minocycline and doxycycline inhibit angiogenesis in vitro by a non-metalloproteinase-dependent mechanism. Brodovsky SC, McCarty CA, Snibson G, et al. Scale bar=50 m. The authors have no commercial or proprietary interest in any concept or product described in this article. Instead, it reduces pain and swelling. Immunohistochemical observation of amniotic membrane patching on a corneal alkali burn in vivo. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. Fluorescence was measured at 412 nm using a Tecan Infinite (M200, Durham, NC) plate reader equipped with Magellan V6.55 software. These 17 Medications May Harm Your Eyes - GoodRx A 50 g/sample was mixed with MPO assay buffer and MPO substrate, incubated at room temperature for 2 hours, and then mixed with tetramethylbenzidine probe. The Wound Healing Effect of Doxycycline after Corneal Alkali Burn in It improved signs and symptoms of KCS, and it is sa This research protocol was approved by the Baylor College of Medicine Center for Comparative Medicine, and it conformed to the standards in the ARVO Statement for the use of animals in Ophthalmic and Vision Research. Effects of the matrix metalloproteinase inhibitor GM6001 on the destruction and alteration of epithelial basement membrane during the healing of post-alkali burn in rabbit cornea. blepharitis or blepharitis associated with rosacea. Doxycycline blocks or inhibits some of the body's responses to infection and inflammation. Federal government websites often end in .gov or .mil. National Library of Medicine Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA. If you are a Mayo Clinic patient, this could The effect of low-dose doxycycline therapy in chronic meibomian gland dysfunction. Gilbertson-Beadling S, Powers EA, Stamp-Cole M, et al. Negligible amounts of MMP-2 were present in all groups (Figure 3C). Conjunctivitis is the most common cause of red eye and is one of the leading indications for antibiotics. Doxycycline Hyclate - Uses, Side Effects, and More - WebMD Howand Whyto Choose Dry Eye Drugs - Review of Optometry A common side effect of isotretinoin is dry eye. Li DQ. Makeup can make it harder to keep your eyelids clean and free of debris. While the common condition can be overwhelming to treat with its many variables and management options, identifying a cause is . Neutrophil gelatinase-associated lipocalin is expressed in osteoarthritis and forms a complex with matrix metalloproteinase 9. Before Click here for an email preview. Oral tetracycline and tetracycline derivatives (e.g., doxycycline, minocycline) can be used to treat DED associated conditions such as rosacea, blepharitis and meibomian gland dysfunction. D. Corneal opacity score in CM corneas topically treated with BSS, Dex, or Doxy. Early topical anti-inflammatory therapy appears to inhibit sight-threatening corneal ulceration and perforation in our mouse model, and these findings support the use of these anti-inflammatory agents in the treatment of human cornea alkali burns. The role of matrix metalloproteinases in ulcerative keratolysis associated with perioperative diclofenac use. Mice subjected to the combined model for 2 and 5 days were topically treated either with 2 L sodium phosphate dexamethasone (Dex, 0.1%, Spectrum Laboratory, Gardena, CA), 2 L of freshly prepared doxycycline USP (Doxy, 0.025%,Sigma-Aldrich, St. Louis, MO) or vehicle (balanced salt solution, BSS, Alcon, Fort Worth, TX) QID and compared to nave control corneas. The results of quantitative PCR were analyzed by the comparative CT method where target change = 2CT. There is a problem with Martin RR, Warr GA, Couch RB, et al. Faurschou M, Borregaard N. Neutrophil granules and secretory vesicles in inflammation. We have used Doxycycline 20mg po qday for years to help decrease eyelid inflammation. Immunohistochemistry was performed to detect neutrophils using rat anti-Gr-1 antibody (Ly6G; 1:250, clone 1A8, BD Pharmingen). Better understanding of these mechanisms might offer the practicing clinicians a better use of this therapeutic tool. Autologous platelet-rich plasma for facial rejuvenation: yes, I think it does help. Accessibility It is known that the epithelial basement membrane is quite resistant to alkali exposure and it is subsequently degraded by MMPs produced by the regenerating epithelium.29 To investigate this, we performed immunofluorescent staining for integrin 4, a component of the basement membrane in eyes that had no perforation. 2022 Dec;39(6):1101-1105. doi: 10.5114/ada.2022.119008. One of the key questions we have long had is the effect of Doxycyline on gut flora and resistance. We also harvested mouse eye samples 21 days after PVR induction to examine the retinas using hematoxylin and eosin (H&E) staining and found that the cellular arrangement of the retinas with PVR was disrupted (Figure 3 C . Doxycycline treatment promoted corneal healing and reduced corneal opacity in SD rats. It is well recognized that alkali burns to the cornea induce a severe inflammation and MMP production.16,26 We have previously reported that inhibition of tear production and exposure to a desiccating environment markedly worsened corneal inflammation and matrix degradation, leading to perforation in nearly 30% of corneas acutely subjected to alkali burn.20 Here we report that although topical therapy with broad anti-inflammatory agents (doxycycline and dexamethasone) decreased corneal perforations, production and activation of MMPs, and neutrophil infiltration, these two prototype drugs have differential activity.