Effect of autologous serum after amniotic membrane transplantation for persistent corneal ulcers

AIM:To investigate the effect of adding autologous serum eye drops to the postoperative regime after amniotic membrane transplantation for severe persistent corneal ulcers.METHODS:Forty eyes of 40 patients with persistent corneal ulcers were randomly assigned to artificial tears(sodium hyaluronate 0.2%,ATs group,n=20)or autologous serum eye drops(ASEDs,n=20)following treatment with amniotic membrane transplantation.Digital slit lamp images were acquired from all patients before and 30d post treatment.The area with fibrovascular tissue was calculated using Image J.Central corneal sensitivity was assessed by Cochet-Bonnet aesthesiometry before and one month after treatment.Scar tissue transparency was assessed with a novel optical densitometry.RESULTS:Mean age of patients was 61.65±16.47y and 57.3±19.11y in the ATs group and ASEDs group,respectively.Twenty-two male and 18 female patients were included in the study.The improvement in visual acuity was significantly greater in the ASEDs group(0.14±0.04)than the ATs(0.08±0.04;P=0.00046).Cochet-Bonnet aesthesiometry improved significantly after treatment with a similar rate between groups.There were no statistically significant differences in the area of postoperative fibrovascular tissue between the two groups(P=0.082).The success rate in the two groups was similar.The difference in densitometry between the ATs and ASEDs group was statistically significant(P=0.042)with greater reduction from baseline in the ASEDS group.CONCLUSION:Autologous serum eye drops can lead to better visual acuity,more stable results and improved densitometry and should be considered in the postoperative care following amniotic membrane transplantation.

Changes in interleukin-6 tear concentration and clinical outcome in moderate-to-severe bacterial corneal ulcers after corneal collagen cross-linking

We aimed to evaluate interleukin-6（IL-6） tear concentration and clinical outcome in patients with moderate-to-severe bacterial corneal ulcers post corneal collagen cross-linking（CXL） therapy. This pre-post designed study involving 21 moderate-to-severe corneal ulcer patients who underwent CXL therapy. Patients with infectious corneal ulcer were given CXL therapy as adjunctive treatment after 5 d of broadspectrum antibiotic treatment. Patients with moderate to severe infectious bacterial corneal ulcers were included in this study. Tear sampling was performed before CXL therapy, using sterile Schimer paper from conjunctival inferior fornix. CXL therapy was performed in accordance with the CXL Dresden protocol. Data recording and tear sampling were then performed at day 1 and day 7 after CXL therapy. Data recording included, presence of conjunctival hyperemia, visual analogue scale（VAS）, size of corneal defects, and decemetocele. There was a decrease in IL-6 tear concentration by day 7 after CXL therapy（P=0.001）. IL-6 concentration at 1 h after therapy（2274.67±2120.46 pg/m L） tended to be lower than before therapy（4330.09±3169.70 pg/m L）, but the difference was not statistically significant（P=0.821）. The size of corneal defects decreased significantly post CXL（P=0.007）. The log MAR visual acuity before and after CXL therapy was not found to be significantly different（P=0.277）. There was a significant decrease in VAS values（P=0.018） and blepharospasm（P=0.011） pre and post CXL. There was no significant decrease in conjunctival hyperemia pre and post CXL（P=0.293）. There was significant reduction in IL-6 tear concentration and clinical improvement in moderateto-severe bacterial corneal ulcers which underwent CXL therapy.

Small-diameter acellular porcine corneal stroma for peripheral corneal ulceration treatment

AIM:To evaluate the clinical efficacy of small-diameter acellular porcine corneal stroma(SAPS)for the treatment of peripheral corneal ulceration(PCU).METHODS:This retrospective clinical study included 18 patients(18 eyes)with PCU between April 2018 and December 2020.All patients had PCU and underwent lamellar keratoplasty with SAPS.Observation indicators included preoperative and postoperative best-corrected visual acuity(BCVA)and transparency of SAPS.The infection control rate in the surgical eye-lesion area was also calculated.RESULTS:Eighteen patients underwent lamellar keratoplasty with SAPS to treat PCU.None of the patients experienced rejection after 6mo(18/18)and 12mo(16/16)of follow-up.The BCVA(0.47±0.30)at the 6mo followup after operation was significantly improved compared with the baseline(0.99±0.80),and the difference was statistically significant(Z=-3.415,P<0.05).The BCVA at the 12mo follow-up after operation was not statistically significant compared to the 6mo(Z=0,P=1).With time,the SAPS graft gradually became transparent.At the 6mo(18/18)and 12mo(16/16)follow-up,none of the patients had recurrent corneal infection.CONCLUSION:SAPS is clinically effective in the treatment of PCU,improving the patient’s BCVA and reducing the incidence of rejection after keratoplasty.

Molecular mechanism of the inhibition effect of Celecoxib on corneal collagen degradation in three dimensions

AIM: To clarify the molecular mechanism of Celecoxib on corneal collagen degradation and corneal ulcer. METHODS: Rabbit corneal fibroblasts were harvested and suspended in serum-free MEM. Type I collagen, DMEM, collagen reconstitution buffer and corneal fibroblast suspension were mixed on ice. The resultant mixture solidify in an incubator, after which test reagents and plasminogen was overlaid and the cultures were returned to the incubator. The supernatants from collagen gel incubations were collected and the amount of hydroxyproline in the hydrolysate was measured. Immunoblot analysis of MMP1, 3 and TIMP1, 2 was performed. MMP2, 9 was detected by the method of Gelatin zymography. Cytotoxicity Assay was measured. RESULTS: Celecoxib inhibited corneal collagen degradation in a dose and time manner; Celecoxib inhibited the IL-1 beta induced increases in proMMP1, 2, 3, 9 and active MMP1, 2, 3, 9 in a concentration-depended manner. Celecoxib can also inhibit the IL-1 beta induced increases in the TIMP1, 2. CONCLUSION: Celecoxib can inhibit corneal collagen degradation induced by IL-1 beta, this effect is the consequence of the reduction of MMP1, 2, 3, 9 and TIMP1, 2. The results of the present study provide new insight into Celecoxib in cornela ulcer treatment.

Corneal ulcer caused by nocardia brasiliensis in a patient with diabetes

Dear Sir,Iam Dr.Sheng-Li Mi,from the Biomanufacturing engineering laboratory,Graduate School at Shenzhen,Tsinghua University,Shenzhen,China.I write to present a case report of nocardia brasiliensis in a patient with diabetes.Nocardia is part of a group of aerobic actinomycetes,widely distributed in soil.Nocardia asteroids and nocardia brasiliensis are the most common human pathogens.Humans infected by nocardia asteroids through the respiratory tract mainly suffer from primary suppurative pulmonary conditions.Infection of nocardia brasiliensis often occurs in the advanced stages of a progressive disease or immune disorder,especially Cushing syndrome,diabetes,or in patients using corticosteroids,immunosuppressive agents and broad-spectrum antibiotics for long time[1].To our knowledge,the reports of nocardia keratitis was very rare

Management of corneal ulceration with a moisture chamber due to temporary lagophthalmos in a brain injury patient:A case report

BACKGROUND This study describes the use of a moisture chamber to treat corneal ulceration due to temporary lagophthalmos in a critically ill patient.CASE SUMMARY A 46-year-old woman was admitted to the intensive care unit after a car accident.She suffered multiple injuries that included brain injury and presented with moderately decreased consciousness and lagophthalmos in her right eye.Within 6 d,her consciousness improved considerably;at which time,exposure keratopathy occurred and worsened to corneal ulceration.Lubricating gel,antibiotic ointment,and bandage contact lens were all ineffective in preventing or treating the exposure keratopathy.Instead of tarsorrhaphy,a moisture chamber was applied which successfully controlled the corneal ulceration.The moisture chamber was discontinued when complete eyelid closure recovered a week later.CONCLUSION A moisture chamber may be an effective,noninvasive alternative to tarsorrhaphy for treating severe exposure keratopathy due to temporary lagophthalmos.

Amniotic membrane transplantation in a patient with impending perforated corneal ulcer caused by Streptococcus mitis: A case report and review of literature

BACKGROUND Streptococcus mitis(S.mitis)is an opportunistic pathogen that can lead to severe ocular infections.In previous reports,penetrating keratoplasty(PK)was usually adopted for the treatment of persistent corneal ulcers.This report describes an unusual case of nonhealing descemetocele caused by S.mitis treated by antibiotics plus amniotic membrane transplantation(AMT).CASE SUMMARY A 63-year-old woman presented with a right persistent corneal ulcer that she had suffered from for the past 9 mo.The culture of a corneal scraping yielded S.mitis.The right eye descemetocele decreased in diameter from 3 to 0.8 mm after the continuous administration of topical vancomycin and ceftriaxone for 2 wk.Due to the slow healing,AMT was performed.Her corneal erosion healed and gradually became clear.Her visual acuity recovered from initially counting fingers to 100/200 at the last follow-up,67 mo after AMT.CONCLUSION Antibiotics plus AMT may be an effective alternative treatment other than PK to promote epithelializationand to reduce inflammation in the corneas complicated by S. mitis keratitis.

Effect of Topical FK506 Used alone or Combined with Keratoplasty on Patients with Recurrent Mooren′s Corneal Ulcer

Purpose: To evaluate the efficacy of topical 0.1% FK506 used alone or combined with keratoplasty on patients with recurrent Mooren′s ulcer. Methods: This is a retrospective interventional consecutive case series. Nine patients (15 eyes) with recurrent Mooren′s ulcer were treated with topical 0.1% FK506 alone or combined with keratoplasty. Two eyes with ulcers involving less than half the corneal limbus were treated with topical 0.1% FK506. Of the other 13 eyes with ulcers involving more than half the limbus, twelve were treated with excision of the ulcer and adjacent conjunctiva combined with lamellar keratoplasty. One eye with a central impending corneal perforation was treated with penetrating keratoplasty.Topical 0.1% FK506 was given post-operatively to all thirteen eyes after re-epithelia-lisation of the cornea. FK506 levels in the surgically resected cornea and conjunctiva of the operated eyes were measured using enzyme immunoassay procedures. Twelve patients (17 eyes) with recurrent Mooren′s ulcer treated with lamellar keratoplasty combined with topical 0.1% dexamethasone were taken as the control. The main measure of the outcome was the recurrence of Mooren′s ulcer in the patients. Results: Nine patients (15 eyes) with recurrent Mooren′s ulcer were all successfully treated. Vision in 5 eyes improved by two lines or better after treatment. No recurrence was observed during the follow up period of 12 to 22 months. After topical application of 0.1% FK506, concentrations of 30～350 ng/g of FK506 were found in the cornea and conjunctiva. Seven eyes of Mooren′s ulcer in the control group recurred during the follow up period. Conclusion: Topical 0.1% FK506 used alone or combined with keratoplasty is a safe and effective therapy for patients with recurrent Mooren′s ulcer.

A Rare Association of Giant Cell Arteritis with Recurrent Corneal Ulcer

We report a rare case of association of temporal arteritis with recurrent central corneal ulcer. A 91-year-old male with a remote history of clinically diagnosed giant cell arteritis (GCA) and penetrating keratoplasty (PK) for corneal edema in 1990’s in the left eye presented with irritation and severe dry eye. He progressively developed central corneal ulcer regardless of treatment with aggressive lubrication and patching. The clinical course, blood tests and temporal artery biopsy results yielded the diagnosis of recurrent GCA. The clinical course improved after starting oral steroids. The case report illustrates the importance of ruling out GCA in patients with recurrent corneal ulcers and history of GCA. It also highlights the significance of shared understanding between primary care physicians and specialists to handle common and chronic diseases to make efficient diagnoses and plan treatment regimens. This is the first plausible case of reported GCA association with central corneal ulcer in the United States.

Keeping an eye on the diabetic foot: The connection between diabetic eye disease and wound healing in the lower extremity

Diabetic eye disease is strongly associated with the development of diabetic foot ulcers(DFUs).DFUs are a common and significant complication of diabetes mellitus(DM)that arise from a combination of micro-and macrovascular compromise.Hyperglycemia and associated metabolic dysfunction in DM lead to impaired wound healing,immune dysregulation,peripheral vascular disease,and diabetic neuropathy that predisposes the lower extremities to repetitive injury and progressive tissue damage that may ultimately necessitate amputation.Diabetic retinopathy(DR)is caused by cumulative damage to the retinal microvasculature from hyperglycemia and other diabetes-associated factors.The severity of DR is closely associated with the development of DFUs and the need for lower extremity revascularization procedures and/or amputation.Like the lower extremity,the eye may also suffer end-organ damage from macrovascular compromise in the form of cranial neuropathies that impair its motility,cause optic neuropathy,or result in partial or complete blindness.Additionally,poor perfusion of the eye can cause ischemic retinopathy leading to the development of proliferative diabetic retinopathy or neovascular glaucoma,both serious,visionthreatening conditions.Finally,diabetic corneal ulcers and DFUs share many aspects of impaired wound healing resulting from neurovascular,sensory,and immunologic compromise.Notably,alterations in serum biomarkers,such as hemoglobin A1c,ceruloplasmin,creatinine,low-density lipoprotein,and highdensity lipoprotein,are associated with both DR and DFUs.Monitoring these parameters can aid in prognosticating long-term outcomes and shed light on shared pathogenic mechanisms that lead to end-organ damage.The frequent cooccurrence of diabetic eye and foot problems mandate that patients affected by either condition undergo reciprocal comprehensive eye and foot evaluations in addition to optimizing diabetes management.

Modified ulcer debridement in the treatment of the superficial fungal infection of the cornea

AIM： To evaluate the efficacy of modified corneal ulcer debridement in superficial fungal keratitis unresponsive to medications.METHODS： A total of 209 patients（209 eyes） with fungal keratitis, involving no more than 50% of the stromal depth and not responding to antifungal agents for 2 wk, were recruited in this retrospective, noncomparative study. The patients were treated with modified corneal ulcer debridement. All visible corneal infiltrates were removed under an operating microscope to obtain a clean stromal bed and smooth incised edges. Antifungal drugs were used immediately after surgery. Healing time of the ulcers was recorded. Fungal recurrence, visual acuity, corneal thickness and risk factors for treatment failure were monitored.RESULTS： The follow-up was 13.6±5.8m o. The corneal ulcers healed in 195 of 209 eyes（93.3%）, with a mean healing time of 8.4±6.8 d. The other 14 eyes were further treated by penetrating keratoplasty（PK）（1 eye）, anterior lamellar keratoplasty（LK）（7 eyes）, conjunctival flap covering（4 eyes） or amniotic membrane transplantation（2 eyes）. The best corrected visual acuity（BCVA） was ≥20/70 in 80.3% of the eyes, ≥20/40 in 56.9% of the eyes, and ≥20/25 in 27.3% of the eyes. The corneas at the lesions became thinner, but all in the safe range. No fungal recurrence or corneal ectasis developed during the follow-up. The risk of treatment failure was higher in patients with preoperative hypopyon（P=0.036） and ever using steroid（P=0.025）.CONCLUSION： Modified surgical debridement is a simple and effective method for the treatment of superficial fungal infection of the cornea, with improved visual acuity and no recurrence. Such an intervention in time can rapidly control fungal infection and largely shorten corneal ulcer healing time.

Studies on Free Radical EPR,Superoxide Dismutase Water-soluble Lipidperoxide in Tears

By means of electron paramagnetic resonance(EPR), chemistry luminescence and fluorescent spectroscopy, the free radical, superoxide dismutase and water soluble lipid peroxide in tears of normal eyes(150 eyes, 100 cases), Moorens ulcer(9 eyes), coreal grafts rejection(16 eyes) were studied. The results showed that the spin density of the free radical was 36(±058)×1012 spins/mL tear, the content of the superoxide dismutase(SOD) was 384(±145) ng/mL tear, the opposite fluorescent density of the water soluble lipid peroxide was 12912(±1691) U/mL tear in normal tears. The normal values are 25—48×1012 spins/mL tear for free radical, 239—529 ng/mL tear for SOD, 9598—16225 U/mL tear for water soluble lipid peroxide. There are significant differences in different eyes, different sexes and different ages. The free radical and lipid peroxide are higher obviously in the tears of patients with Moorens ulcer and rejected corneal grafts, compared with those of the normal control subjects(P<001), SOD is lower evidently(P<001). The above fact shows the pathogenic mechanism of Moorens ulcer and keractoplasty rejection is significantly related to toxicities injuring effect of the free radical. These results have provided important experimental data for studying lacrimalogy and new methods for clinical diagnosis and treatrment.

Shifting hierarchy of the conjunctival florae in the patients employed a long-time topical fluoroquinolone

AIM:To observe the shifting hierarchy of the conjunctival florae in the patients who employed a long-time topical fluoroquinolone and characterize the consequent variations of their antibiotic sensitivity and virulence.METHODS:A total of 143 eyes(143 patients)who suffered from the non-infectious corneal ulcer and topically used fluoroquinolone more than 2 wk were enrolled as the fluoroquinolone eye.The untreated fellow eye was considered as the contralateral eye.Seventy-five healthy subjects were selected as the control.The culture positivity and strains of the isolated conjunctival florae were observed.Their antibiotic susceptibility and expression of the virulence-related genes were detected.RESULTS:Florae were recovered from 84.0%,37.1%,and 57.3%of the conjunctival swabs in the control,fluoroquinolone eye,and contralateral eye,respectively.The most frequently isolated microorganisms were Staphylococcus epidermidis(34.9%)in the control,followed by Staphylococcus aureus(17.5%),Staphylococcus saprophyticus(14.3%),Micrococcus(9.5%),Propionibacterium acnes(7.9%).However,those orderly ranks shifted to Staphylococcus aureus(34.0%),Propionibacterium acnes(20.8%),Candida albicans(17.0%),Pseudomonas aeruginosa(9.4%)in the fluoroquinolone eye.A growing number of the fluoroquinolone-resistant florae survived in the fluoroquinolone eye,accompanied by an increased expression of the virulence-related genes.CONCLUSION:A long-time topical fluoroquinolone leads to a shifting hierarchy of the conjunctival florae,accompanied by the consequent variations of the antibiotic sensitivity and virulence.

Disseminated Tuberculosis Presenting with Scrofuloderma and Anterior Staphyloma in a Child in Sokoto, Nigeria

Introduction: Disseminated tuberculosis (TB) may occur with skin and ocular involvement which are not common manifestations in children and may lead to debilitating complications. Objective: A child with multi-organ TB involving the lungs, chest abdomen, skin and eyes who had been symptomatic for 3 years is reported. Case Report: A 6-year-old girl presented with recurrent fever, abdominal pain and weight loss of 3 years and skin lesions of a year duration. There was history of pain and redness of the eyes associated with discharge. She was not vaccinated at all. She was chronically ill-looking with bilateral conjunctival hyperaemia, purulent eye discharge with corneal opacity of the right eye. She had significant lymphadenopathy, digital clubbing and ulcerated, discharging swellings around her neck and axilla (scrofuloderma). She had reduced breath sounds and coarse crepitations. Hepatosplenomegaly and ascites were present. She later developed bulging of the upper part of the cornea of the right eye which was diagnosed by the ophthalmologist to be cornea ulcer with anterior staphyloma. Results, Treatment and Outcome: Complete blood count (leucocytosis 12,800 cells), erythrocyte sedimentation rate (150 mm/hr) and tuberculin test (7 mm induration) were suggestive of TB. Radiological tests were also supportive. She received anti-Kochs in addition to systemic and ocular antibiotics. Skin lesions healed progressively and stopped discharging. Caregivers were counseled on poor visual prognosis of the right eye. She was discharged but lost to follow up. Conclusion: Multi-organ involvement of TB especially ocular and cutaneous TB is not common but is very debilitating. More preventive efforts with vaccination and expertise are needed at lower levels of health care in the community to aid early diagnosis.

Orthokeratology lens related infections

Orthokeratology is a reversible technique that temporarily changes the curvature of the cornea with the aim of addressing refractive errors. The United States Food and Drug Administration(FDA) granted approval for using reverse geometry contact lenses to correct myopia without any age restriction. Information from the pre-market applications to the FDA was rated as level Ⅱ evidence. Another unapproved use of overnight orthokeratology is for the prevention of myopic progression. Although orthokeratology is advocated to reduce myopic progression, there are limited long-term studies with substantial evidence of its benefits. Much of this evidence comes from non-robust experimental studies using historical or self-selected controls with relative high dropout rates. Although some positive results have been published in temporarily reducing the myopic refractive error and its progression, the use of these lenses can be associated with serious complications such as microbial keratitis. Microbial keratitis is a potentially vision-threatening adverse response associated with contact lens wear. In fact, contact lens wearhas been shown to be the predominant risk factor of microbial keratitis in some developed countries. Most of the published cases on overnight orthokeratology related microbial keratitis occurred in children or adolescents. Parents considering orthokeratology must make an informed decision about its temporary benefit and its potential for permanent loss of vision. The ophthalmic community should be reminded of the potential complications of orthokeratology.

A Novel Tectonic Keratoplasty with Femtosecond Laser ntrastromal Lenticule for Corneal Ulcer and Perforation

Background： Small incision refractive lenticule extraction （SMILE） is an effective laser procedure that treats myopia. This research was to describe a novel approach to treat corneal ulcer or perforation using the corneal lenticules obtained from SMILE and to evaluate the safety and effectiveness of tectonic keratoplasty with femtosecond laser intrastromal lenticule （TEKIL）. Methods： A total of twenty patients （22 eyes） were monitored for at least 6 months and were assessed using slit lamp microscopy, optical coherence tomography, and best-corrected visual acuity （BCVA）. Postoperative complications throughout the study period were recorded. Results： Corneal ulcer in 14 patients （16 eyes） and corneal perforation in six patients （6 eyes） were treated with TEKIL. The patients were ten females and ten males, with a mean age of 58.5 ± 16.3 years （range： 16 81 years）. In this study, the most causes of corneal ulcer or perforation were immunologic causes （54.5%）. After TEKIL procedure, global integrity was achieved in all cases. No immune rejection or perforation was detected. The mean BCVA improved from 0.17± 0.20 preoperatively to 0.27 ± 0.25 postoperatively at the final follow-up （t = 2.095, P 0.052）. The postoperative BCVA improved in 12 eyes （54.5%） and maintained in nine eyes （40.9%）. Vision function successfully maintained in all eyes （100%）. In three cases, corneal ulcers were treated by reoperation of TEKIL at 3 months alter the initial surgery for the reason that the residual corneal thickness was 〈250 μm. Conclusions： TEKI L seems to be an effective treatment for corneal ulcer and perforation in the condition of emergency and donor shortage.

PACK-CXL: Corneal cross-linking in infectious keratitis

Background:Corneal cross-linking(CXL)using ultraviolet light-A(UV-A)and riboflavin is a technique developed in the 1990’s to treat corneal ectatic disorders such as keratoconus.It soon became the new gold standard in multiple countries around the world to halt the progression of this disorder,with good long-term outcomes in keratometry reading and visual acuity.The original Dresden treatment protocol was also later on used to stabilize iatrogenic corneal ectasia appearing after laser-assisted in situ keratomileusis(LASIK)and photorefractive keratectomy(PRK).CXL efficiently strengthened the cornea but was also shown to kill most of the keratocytes within the corneal stroma,later on repopulated by those cells.Review:Ultraviolet-light has long been known for its microbicidal effect,and thus CXL postulated to be able to sterilize the cornea from infectious pathogens.This cytotoxic effect led to the first clinical trials using CXL to treat advanced infectious melting corneal keratitis.Patients treated with this technique showed,in the majority of cases,a stabilization of the melting process and were able to avoid emergentàchaud keratoplasty.Following those primary favorable results,CXL was used to treat beginning bacterial keratitis as a first-line treatment without any adjunctive antibiotics with positive results for most patients.In order to distinguish the use of CXL for infectious keratitis treatment from its use for corneal ectatic disorders,a new term was proposed at the 9th CXL congress in Dublin to rename its use in infections as photoactivated chromophore for infectious keratitis-corneal collagen cross-linking(PACK-CXL).Conclusion:PACK-CXL is now more frequently used to treat infections from various infectious origins.The original Dresden protocol is still used for this purpose.Careful modifications of this protocol could improve the efficiency of this technique in specific clinical situations regarding certain types of pathogens.