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1.
Cornea ; 41(3): 280-285, 2022 03 01.
Article in English | MEDLINE | ID: mdl-34176918

ABSTRACT

PURPOSE: The purpose of this study was to assess cryopreserved amniotic membrane (C-AM) versus chorion-free freeze-dried amniotic membrane (FD-AM) overlay transplantation for corneal ulcers in a French tertiary ophthalmology hospital. METHODS: Between March and July 2020, when C-AMs were not available because of the COVID-19 pandemic, 28 corneal ulcers underwent FD-AM overlay transplantation and were retrospectively compared with 22 corneal ulcers treated with C-AM during the same period in 2018. All patients had at least 3 months of follow-up, and those who underwent combined surgeries were excluded. Ulcers were assessed at baseline and then at 72 hours, 1 month, and 3 months. Population demographics, follow-up time, ulcer etiologies, epithelial defect size, ulcer depth, and complications were also recorded. RESULTS: Baseline characteristics and clinical features of both groups were comparable. There was no statistically significant difference in the number of overlay AM transplantations (P = 0.52) or early detachments (P = 0.57). At 3 months, the corneal healing rate was almost the same in both groups (89% and 91% for FD-AM and C-AM, respectively; P = 0.87). Complications were equally uncommon (11% and 9%, respectively; P = 0.92). In logistic regression, the type of the membrane did not influence corneal healing at 1 month (P = 0.42) or 3 months (P = 0.99), regardless of the depth of the ulcer. However, whatever the type of AM used, the deeper the ulcer was, the less likely it was to heal at 3 months (P = 0.02). CONCLUSIONS: This is the first study that provides positive insight into the effectiveness of FD-AM compared with C-AM when used as overlay transplantation for treating corneal ulcers.


Subject(s)
Amnion/transplantation , Corneal Ulcer/surgery , Cryopreservation , Freeze Drying , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , Case-Control Studies , Corneal Ulcer/physiopathology , Female , France/epidemiology , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Wound Healing/physiology
2.
Exp Eye Res ; 204: 108458, 2021 03.
Article in English | MEDLINE | ID: mdl-33493475

ABSTRACT

Peripheral ulcerative keratitis (PUK) is a progressive peripheral thinning of the corneal stroma caused by proinflammatory mediators' release from corneal limbal vasculitis. The clinical presentation is an epithelial defect with a crescent-shaped stromal inflammation. Its exact pathophysiologic mechanisms of PUK remain partially understood, but the overall understanding of the fundamental processes that mediate and effect corneal immunity has continued to expand over the past 25 years. The unique anatomical and physiological characteristics of the periphery in relation to collagen bundles and peripheral corneal vascular arch contribute to the occurrence of this type of ulcer in this region, in addition to the concentration of complement and immunoglobulins. There is a relevant participation of the adjacent conjunctiva. Both cell-mediated immunity and humoral immunity are implicated in the pathogenesis of PUK, and the postulated mechanisms are autoimmune reactions to corneal antigens, deposition of circulating immune complexes and hypersensitivity reactions to foreign antigens. These immunocomplexes are deposited in limbic vessels resulting in the activation of the classical pathway of the complement system and, consequently, in the chemotaxis of inflammatory cells and in the release of several pro-inflammatory cytokines, which allow the production and release of matrix metalloproteinases. The release of inflammatory cytokines by infiltrating cells may induce keratocyte activation, which could then generate more release of a variety of cytokines, such as the neutrophil calgranulin C, thus facilitating an autoimmune response to the protein and precipitating an antibody- and cell-mediated hyperimmune reaction in the peripheral cornea.


Subject(s)
Corneal Ulcer/immunology , Immunity, Cellular/physiology , Immunity, Humoral/physiology , Autoimmunity , Corneal Stroma/pathology , Corneal Ulcer/diagnosis , Corneal Ulcer/physiopathology , Humans , Limbus Corneae/pathology , Vasculitis/pathology
3.
Curr Eye Res ; 46(6): 771-776, 2021 06.
Article in English | MEDLINE | ID: mdl-33151784

ABSTRACT

Purpose: To unveil the long-term prognosis of Acanthamoeba keratitis based on clinical presentation and timing of diagnosis to better inform patients since the first visit regarding their length of treatment, quality of life, and visual function.Methods: Retrospective observational study enrolling patients with Acanthamoeba keratitis from 1994 to 2019. Patients with a complete eye examination and medical records were analyzed. The severity of the disease, the time from onset of symptoms to the appropriate therapeutic regimen, the time until clinical resolution, visual function, and long term follow-up was evaluated. Quality of life was assessed at the last follow-up visit by means of the VFQ-25 questionnaire.Results: Thirty-five patients (40 eyes) were assessed. The overall healing time of patients with Acanthamoeba keratitis was 12.5 ± 3.5 months, while patients with a severe corneal ulcer (stage III) had a significant longer healing time (16.2 ± 3.7 months) compared to patients with stage II (7.04 ± 0.7 months) or I (7.7 ± 1.5 months; p < .05). Patients who received a prompt therapy (<30 days form symptoms onset) had a reduced healing time compared to patients with a delayed diagnosis (p < .01). Quality of life was assessed after a mean of 11.7 ± 4.7 years and it was mildly reduced (86.6 ± 17). Patients that were diagnosed early (<30 days from onset) showed a lower reduction in quality of life than in patients that were diagnosed >30 days from onset. After resolution, 59% of the patients considered unnecessary any further proposed surgical intervention.Conclusions: Delayed diagnosis of Acanthamoeba keratitis and disease severity significantly increases healing time and duration of treatment. The time to diagnosis and disease stage at diagnosis predicts the duration of treatment, the final outcome, quality of life, and the requirement of surgery. These data would allow us to promptly inform patients about long-term disease timeline, future outcomes, improving disease acceptance, and quality of life.


Subject(s)
Acanthamoeba Keratitis/diagnosis , Acanthamoeba Keratitis/physiopathology , Acanthamoeba Keratitis/drug therapy , Acanthamoeba Keratitis/psychology , Adolescent , Adult , Aged , Antiprotozoal Agents/therapeutic use , Benzamidines/therapeutic use , Biguanides/therapeutic use , Child , Contact Lenses/adverse effects , Corneal Ulcer/physiopathology , Corneal Ulcer/psychology , Disinfectants/therapeutic use , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Prognosis , Quality of Life/psychology , Retrospective Studies , Risk Factors , Time Factors , Visual Acuity/physiology , Wound Healing/physiology , Young Adult
4.
Cornea ; 40(5): 618-623, 2021 May 01.
Article in English | MEDLINE | ID: mdl-33055550

ABSTRACT

PURPOSE: To report the indications, long-term structural and functional outcomes, and prognostic factors for the success of penetrating and lamellar corneal patch grafts. METHODS: This is a retrospective analysis of 49 patients who underwent the corneal patch graft procedure over 8 years. The baseline, preoperative, and postoperative characteristics along with their outcomes were evaluated. RESULTS: Forty-nine eyes (49 patients) with a mean follow-up of 20.3 ± 3.27 months (range 6-48) were included. Thirty-one patients underwent full-thickness grafts for corneal perforation, and 18 underwent lamellar grafts for severe thinning. The most common indication was corneal thinning and/or perforation secondary to microbial keratitis (17 eyes, 34.7%). Anatomic success was achieved in 31 eyes (63.2%), in which no further surgical intervention was required for tectonicity. Functional success was achieved in 22 of 37 eyes (59.5%), where along with anatomic success, significant visual gain was also obtained. Absolute graft failure was noted in 12 eyes (24.5%), which developed recurrence of primary pathology requiring reintervention within the first 6 months. Good prognostic factor for success included sterile corneal perforations. The presence of microbial keratitis was noted to be a guarded prognostic factor for success. CONCLUSIONS: Corneal patch graft can serve as a good therapeutic modality for corneal ulceration or thinning, not amenable to treatment with tissue adhesive application. Both anatomical success and functional success of 60% was achieved in our series. Those performed for immune-mediated conditions fared the best. Subsequent optical procedures may be performed for further visual rehabilitation at a later stage.


Subject(s)
Corneal Perforation/surgery , Corneal Transplantation , Corneal Ulcer/surgery , Keratoplasty, Penetrating , Adult , Corneal Perforation/physiopathology , Corneal Ulcer/physiopathology , Female , Follow-Up Studies , Graft Rejection/diagnosis , Graft Survival/physiology , Humans , Male , Middle Aged , Postoperative Complications , Retrospective Studies , Slit Lamp Microscopy , Treatment Outcome , Ultrasonography , Visual Acuity/physiology , Young Adult
5.
Cornea ; 40(1): 5-11, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33038155

ABSTRACT

PURPOSE: With very photophobic patients, the advantages of red or near infrared light to develop new ophthalmology imaging devices seem obvious: no or little glare, possibility of long signal integration, no phototoxicity, and lesser autofluorescence of ocular tissues. Nevertheless, in this range, the shortest possible wavelength facilitates signal detection. The aim of this study was, thus, to determine the maximal irradiance tolerated with 6 wavelengths: 2 red, 2 far red, and 1 near infrared lights to determine the shortest wavelength well tolerated by patients, in comparison with the standard cobalt blue light of ophthalmology slitlamp. METHODS: An interventional, monocentric, single-group assignment study was conducted on 30 eyes of 30 patients with infectious keratitis. Thanks to a customized machine, the photophobic eye was exposed to the 6 lights with increasing intensity. The patients switched off the light when the discomfort was too elevated. The maximal cumulative irradiance possible at 482, 650, 675, 700, 750, and 800 nm were 171, 689, 759, 862, 920, and 889 mW/cm, respectively. RESULTS: The maximal cumulative irradiance tolerated by patients increased significantly with wavelength (P < 0.001), but the difference was not significant between each increment: red at 675 nm gave a significantly higher cumulative irradiance than blue at 482 nm; red at 700 nm did not provide significant gain compared with 675 nm; and far red at 750 nm still provided additional gain compared with 700 nm, but no significant gain was observed between 750 and 800 nm. The shortest wavelengths were stopped more quickly, and more than 50% of patients reached the maximum irradiance delivered by the source at 750 and 800 nm. CONCLUSIONS: We demonstrate that a light source at 750 and 800 nm can be used for ophthalmic imaging with good tolerance in photophobic patients. CLINICAL TRIAL REGISTRATION: NCT03586505.


Subject(s)
Corneal Ulcer/radiotherapy , Eye Infections, Bacterial/radiotherapy , Light , Neisseriaceae Infections/radiotherapy , Photophobia/radiotherapy , Pseudomonas Infections/radiotherapy , Slit Lamp Microscopy/instrumentation , Adolescent , Adult , Aged , Aged, 80 and over , Corneal Ulcer/physiopathology , Eye Infections, Bacterial/diagnosis , Eye Infections, Bacterial/physiopathology , Female , Humans , Lighting , Male , Maximum Tolerated Dose , Middle Aged , Models, Theoretical , Neisseriaceae Infections/diagnosis , Neisseriaceae Infections/physiopathology , Photophobia/physiopathology , Pseudomonas Infections/diagnosis , Pseudomonas Infections/physiopathology , Radiotherapy Dosage
6.
Cornea ; 40(7): 837-841, 2021 Jul 01.
Article in English | MEDLINE | ID: mdl-33079921

ABSTRACT

PURPOSE: To determine whether there is a benefit to adjuvant corneal cross-linking (CXL) for bacterial keratitis. METHODS: This is an outcome-masked, randomized controlled clinical trial. Consecutive patients presenting with a smear-positive bacterial ulcer at Aravind Eye Hospitals at Madurai, Pondicherry, and Coimbatore in India were enrolled. Study eyes were randomized to topical moxifloxacin 0.5% or topical moxifloxacin 0.5% plus CXL. The primary outcome of the trial was microbiological cure at 24 hours on repeat culture. Secondary outcomes included best spectacle corrected visual acuity at 3 weeks and 3 months, percentage of study participants with epithelial healing at 3 weeks and 3 months, infiltrate and/or scar size at 3 weeks and 3 months, 3-day smear and culture, and adverse events. RESULTS: Those randomized to CXL had 0.60 decreased odds of culture positivity at 24 hours (95% confidence interval [CI]: 0.10-3.50; P = 0.65), 0.9 logarithm of the minimum angle of resolution lines worse visual acuity (95% CI: -2.8 to 4.6; P = 0.63), and 0.41-mm larger scar size (95% CI: -0.48 to 1.30; P = 0.38) at 3 months. We note fewer corneal perforations or need for therapeutic penetrating keratoplasty in the CXL group. CONCLUSIONS: We were unable to confirm a benefit to adjuvant CXL in the primary treatment of moderate bacterial keratitis. However, CXL may reduce culture positivity and complication rates; therefore, a larger trial to fully evaluate this is warranted. TRIAL REGISTRATION: NCT02570321.


Subject(s)
Corneal Ulcer/drug therapy , Cross-Linking Reagents/therapeutic use , Eye Infections, Bacterial/drug therapy , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Aged , Anti-Bacterial Agents/therapeutic use , Bacteria/isolation & purification , Collagen/metabolism , Combined Modality Therapy , Corneal Stroma/drug effects , Corneal Stroma/metabolism , Corneal Ulcer/metabolism , Corneal Ulcer/microbiology , Corneal Ulcer/physiopathology , Eye Infections, Bacterial/metabolism , Eye Infections, Bacterial/microbiology , Eye Infections, Bacterial/physiopathology , Female , Humans , Male , Middle Aged , Moxifloxacin/therapeutic use , Riboflavin/therapeutic use , Treatment Outcome , Ultraviolet Rays , Visual Acuity/physiology
7.
Am J Ophthalmol ; 218: 296-303, 2020 10.
Article in English | MEDLINE | ID: mdl-32717268

ABSTRACT

PURPOSE: To establish the prevalence, clinical characteristics, and risk factors for persistent corneal epithelial defects (PED) in patients with chronic ocular graft-versus-host disease (oGVHD) and to determine visual outcomes after healing. DESIGN: Retrospective cohort study. METHODS: A chart review was conducted of patients in whom chronic oGVHD was diagnosed between January 2011 and December 2018 and their demographic and clinical characteristics were collected. Data were analyzed to determine prevalence of PED, and multivariate logistic regression was performed to determine the risk factors associated with it. RESULTS: A total of 405 patients at a mean age of 60 ± 13 years in whom chronic oGVHD was diagnosed; 58% were men. The prevalence of PED was 8.1%. The median time for PED development after hematopoietic stem cell transplantation was approximately 24 months. Median time to PED resolution was 4.5 weeks after starting therapy. The mean best-corrected visual acuity declined by 2 lines post-PED resolution. The prevalence rates of corneal ulcer and perforation were 6.2% and 4.0%, respectively, over 8 years. Logistic regression analysis, used to determine factors associated with PED, showed diabetes (P = .006), limbal stem cell deficiency (LSCD) (P = .02), filamentary keratitis (P = .02), subconjunctival fibrosis (P = .02), and a higher National Institutes of Health (NIH) oGVHD score (P = .01) were significant risk factors for PED development. CONCLUSIONS: The study found the prevalence rate of PED, corneal ulceration, and corneal perforation in chronic oGVHD to be 8.1%, 6.2%, and 4%, respectively. Analysis showed that oGVHD patients with diabetes, LSCD, filamentary keratitis, subconjunctival fibrosis, and a high NIH score were at higher risk of developing severe corneal disease.


Subject(s)
Corneal Perforation/epidemiology , Corneal Ulcer/epidemiology , Epithelium, Corneal/pathology , Graft vs Host Disease/epidemiology , Adult , Aged , Aged, 80 and over , Chronic Disease , Corneal Perforation/diagnosis , Corneal Perforation/physiopathology , Corneal Ulcer/diagnosis , Corneal Ulcer/physiopathology , Female , Graft vs Host Disease/diagnosis , Graft vs Host Disease/physiopathology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Male , Middle Aged , Prevalence , Retrospective Studies , Risk Factors , Visual Acuity/physiology , Young Adult
8.
Am J Ophthalmol ; 217: 278-286, 2020 09.
Article in English | MEDLINE | ID: mdl-32387431

ABSTRACT

PURPOSE: To evaluate the renewal of corneal nerve structure and function in patients with neurotrophic keratopathy (NK) treated with recombinant human nerve growth factor (rhNGF) eye drops. DESIGN: Prospective, interventional, before-and-after case series. METHODS: This study included 18 patients with NK with a persistent epithelial defect or corneal ulcer, treated with topical rhNGF, and age-matched healthy controls. Patients underwent clinical examination with corneal fluorescein staining, Schirmer 1 tear test, assessment of corneal sensitivity with the Cochet-Bonnet esthesiometer, and morphologic examination of the nerves by in vivo confocal microscopy (IVCM) at baseline and at 4 and 8 weeks of treatment. IVCM analysis was used to assess corneal sub-basal nerve density, number of nerve branches, and the diameter of nerve fibers. RESULTS: A complete resolution of the epithelial defect was observed in all patients within 8 weeks. Schirmer 1 test showed a significant improvement of tear film secretion. Change from baseline in corneal sensation was significant (P < .001) but did not approach that of healthy controls. After 8 weeks of treatment, there was a significant increase in the mean nerve density in affected eyes as compared to baseline (P = .007) as well as in the number of nerve branches (P = .008) and nerve fiber diameter (P = .007). CONCLUSIONS: Topical treatment with rhNGF was effective in promoting complete corneal healing of persistent epithelial defects and corneal ulcers in patients with NK. This was associated with an improvement of corneal sensitivity and an increase of sub-basal nerve density, diameter, and number of nerve branches, indicating improvement in structure and function of corneal nerves.


Subject(s)
Cornea/innervation , Corneal Ulcer/diagnosis , Epithelium, Corneal/pathology , Nerve Fibers/pathology , Nerve Growth Factor/therapeutic use , Aged , Aged, 80 and over , Cornea/pathology , Cornea/physiopathology , Corneal Ulcer/drug therapy , Corneal Ulcer/physiopathology , Female , Humans , Male , Microscopy, Confocal , Middle Aged , Prospective Studies , Recombinant Proteins , Sensation/physiology
9.
Invest Ophthalmol Vis Sci ; 61(5): 26, 2020 05 11.
Article in English | MEDLINE | ID: mdl-32416603

ABSTRACT

Purpose: IFN-stimulated gene (ISG) 15 is a type 1 IFN-induced protein and known to modify target proteins in a manner similar to ubiquitylation (protein conjugation by ISG15 is termed ISGylation). We sought to determine the role of ISG15 and its underlying mechanisms in corneal innate immune defense against Pseudomonas aeruginosa keratitis. Methods: ISG15 expression in cultured human corneal epithelial cells (HCECs) and mouse corneas was determined by PCR and Western blot analysis. Gene knockout mice were used to define the role of ISG15 signaling in controlling the severity of P. aeruginosa keratitis, which was assessed with photographing, clinical scoring, bacterial counting, myeloperoxidase assay, and quantitative PCR determination of cytokine expression. Integrin LFA-1 inhibitor was used to assess its involvement of ISG15 signaling in P. aeruginosa-infected corneas. Results: Heat-killed P. aeruginosa induced ISG15 expression in cultured HCECs and accumulation in the conditioned media. Isg15 deficiency accelerated keratitis progress, suppressed IFNγ and CXCL10, and promoted IL-1ß while exhibiting no effects on IFNα expression. Moreover, exogenous ISG15 protected the corneas of wild-type mice from P. aeruginosa infection while markedly reducing the severity of P. aeruginosa keratitis in type 1 IFN-receptor knockout mice. Exogenous ISG15 increased bacteriostatic activity of B6 mouse corneal homogenates, and inhibition of LFA-1 exacerbated the severity of and abolished protective effects of ISG15 on P. aeruginosa keratitis. Conclusions: Type 1 INF-induced ISG15 regulates the innate immune response and greatly reduces the susceptibility of B6 mouse corneas to P. aeruginosa infection in an LFA-1-dependent manner.


Subject(s)
Corneal Ulcer/immunology , Cytokines/physiology , Eye Infections, Bacterial/immunology , Immunity, Innate/physiology , Pseudomonas Infections/immunology , Ubiquitins/physiology , Animals , Bacterial Load , Blotting, Western , Cells, Cultured , Corneal Ulcer/metabolism , Corneal Ulcer/physiopathology , Cytokines/metabolism , Epithelium, Corneal/metabolism , Eye Infections, Bacterial/metabolism , Eye Infections, Bacterial/physiopathology , Gene Expression Regulation/physiology , Humans , Mice , Mice, Inbred C57BL , Mice, Knockout , Peroxidase/metabolism , Pseudomonas Infections/metabolism , Pseudomonas Infections/physiopathology , Real-Time Polymerase Chain Reaction , Signal Transduction/physiology
10.
Clin Neurol Neurosurg ; 189: 105636, 2020 02.
Article in English | MEDLINE | ID: mdl-31841741

ABSTRACT

OBJECTIVES: To present the clinical picture, the associated complications and the genetic findings of Jordanian patients diagnosed with Congenital insensitivity to pain with anhidrosis (CIPA). PATIENTS AND METHODS: This is a retrospective study including 7 patients diagnosed with CIPA presenting to Jordan University Hospital neurology clinic between 2001 and 2017. RESULTS: Among five families, seven patients were diagnose with CIPA and followed for a period ranging from one month to 6 years. The initial symptom observed in all patients was high fever in the first few days after birth, decreased sensation to pain and decreased sweating were later noted. Poor weight gain, microcephaly and global developmental delay were present in most cases. All patients had tongue ulcerations. Fingers/toes ulcerations were present in 6/7 (86.0 %), hip joint dislocation in 3/7 (43.0 %), chronic arthritis and joint swelling in 6/7 (86.0 %), corneal ulcers in 4/7 (57.1 %) and kidney amyloidosis in 1/7 (13.0 %) of all patients. Death occurred in 4/7 (57.1 %) patients. Consanguinity was present in all families. Mutation analysis revealed three variants in NTRK1 gene. The frameshift (c.1860_1861insT; p.Pro621fs) mutation was common in our series. One patient carried a novel missense mutation (c.2170 G > A; p.Gly724Ser). The third missense mutation (C2125 G > T; p.Val709Leu) was reported in a previous study in one patient. CONCLUSION: This cohort reveals a severe CIPA phenotype necessitating thorough multidisciplinary care and follow up.


Subject(s)
Arthritis/physiopathology , Corneal Ulcer/physiopathology , Developmental Disabilities/physiopathology , Hereditary Sensory and Autonomic Neuropathies/physiopathology , Hip Dislocation, Congenital/physiopathology , Microcephaly/physiopathology , Receptor, trkA/genetics , Skin Ulcer/physiopathology , Adolescent , Body-Weight Trajectory , Child , Child, Preschool , Female , Fingers , Frameshift Mutation , Hereditary Sensory and Autonomic Neuropathies/genetics , Humans , Infant , Infant, Newborn , Jordan , Male , Mutation , Mutation, Missense , Pedigree , Retrospective Studies , Toes , Tongue Diseases/physiopathology , Ulcer/physiopathology , Young Adult
11.
Ophthalmology ; 127(1): 14-26, 2020 01.
Article in English | MEDLINE | ID: mdl-31585826

ABSTRACT

PURPOSE: To evaluate the efficacy and safety of topical cenegermin (recombinant human nerve growth factor) in patients with neurotrophic keratopathy. DESIGN: Multicenter, randomized, double-masked, vehicle-controlled trial. PARTICIPANTS: Patients with neurotrophic persistent epithelial defect with or without stromal thinning. METHODS: The NGF0214 trial, conducted among 11 sites in the United States, randomized 48 patients 1:1 to cenegermin 20 µg/ml or vehicle eye drops, 6 drops daily for 8 weeks of masked treatment. Follow-up was 24 weeks. Safety was assessed in all patients who received study drug. Efficacy was assessed by intention to treat. MAIN OUTCOME MEASURES: The primary end point was healing of the neurotrophic lesion (persistent epithelial defect or corneal ulcer) after 8 weeks of masked treatment. Masked central readers measured neurotrophic lesions in randomized clinical pictures, then assessed healing status conventionally (<0.5 mm of fluorescein staining in the greatest dimension of the lesion area) and conservatively (0-mm lesion staining and no other residual staining). Secondary variables included corneal healing at 4 weeks of masked treatment (key secondary end point), overall changes in lesion size, rates of disease progression, and changes in visual acuity and corneal sensitivity from baseline to week 8. RESULTS: Conventional assessment of corneal healing showed statistically significant differences at week 8: compared to 7 of 24 vehicle-treated patients (29.2%), 16 of 23 cenegermin-treated patients (69.6%) achieved less than 0.5 mm of lesion staining (+40.4%; 95% confidence interval [CI], 14.2%-66.6%; P = 0.006). Conservative assessment of corneal healing also reached statistical significance at week 8: compared to 4 of 24 vehicle-treated patients (16.7%), 15 of 23 cenegermin-treated patients (65.2%) achieved 0 mm of lesion staining and no other residual staining (+48.6%; 95% CI, 24.0%-73.1%; P < 0.001). Moreover, the conservative measure of corneal healing showed statistical significance at week 4 (key secondary end point). Compared to vehicle, cenegermin-treated patients showed statistically significant reductions in lesion size and disease progression rates during masked treatment. Cenegermin was well tolerated; adverse effects were mostly local, mild, and transient. CONCLUSIONS: Cenegermin treatment showed higher rates of corneal healing than vehicle in neurotrophic keratopathy associated with nonhealing corneal defects.


Subject(s)
Cornea/innervation , Corneal Ulcer/drug therapy , Nerve Growth Factor/therapeutic use , Trigeminal Nerve Diseases/drug therapy , Administration, Ophthalmic , Adult , Aged , Aged, 80 and over , Corneal Ulcer/physiopathology , Double-Blind Method , Epithelium, Corneal/drug effects , Epithelium, Corneal/pathology , Female , Fluorophotometry , Follow-Up Studies , Humans , Male , Middle Aged , Nerve Growth Factor/administration & dosage , Nerve Growth Factor/adverse effects , Ophthalmic Solutions , Recombinant Proteins , Treatment Outcome , Trigeminal Nerve Diseases/physiopathology , Visual Acuity/physiology , Wound Healing/drug effects
12.
Adv Exp Med Biol ; 1161: 3-12, 2019.
Article in English | MEDLINE | ID: mdl-31562617

ABSTRACT

Keratitis is a sight-threatening inflammatory condition of the cornea that can be caused by both infectious and non-infectious agents. Physical or chemical trauma are typically related to non-infectious keratitis, which may then become secondarily infected or remain non-infected. Etiology of infectious keratitis is most often associated with bacteria; but viruses, fungi, and parasites are common causative pathogens as well. As a global concern, common risk factors include: systemic immunosuppression (secondary to malnutrition, alcoholism, diabetes, steroid use), previous corneal surgery (refractive corneal surgery, penetrating keratoplasty), extended wear contact lens use, pre-existing ocular surface diseases (dry eye, epithelial defect) and ocular trauma (agriculture- or farm-related) [1-8]. Annual rates of incidence include nearly one million clinical visits due to keratitis in the United States, while it has been reported that roughly two million people develop corneal ulcers in India. Clinically, patients may show signs of eye pain (ranging from mild to severe), blurred vision, photophobia, chemosis and redness. Pathogenesis is generally characterized by rapid progression, focal white infiltrates with underlying stromal inflammation, corneal thinning, stromal edema, mucopurulent discharge and hypopyon, which can lead to corneal scarring, endophthalmitis, and perforation. In fact, corneal opacity is not only a complication of keratitis, but among the leading causes of legal blindness worldwide. Despite that empirical treatment effectively controls most of the pathogens implicated in infectious keratitis, improved clinical outcomes are not guaranteed. Further, if treatment is not initiated in a timely manner, good visual outcome is reduced to approximately 50% of keratitis patients [9]. Moreover, resultant structural alterations, loss of tissue and an unresolved host response remain unaddressed through current clinical management of this condition.


Subject(s)
Eye Infections , Keratitis , Lipid Metabolism/physiology , Corneal Ulcer/epidemiology , Corneal Ulcer/etiology , Corneal Ulcer/physiopathology , Eye Infections/complications , Eye Infections/microbiology , Eye Infections/parasitology , Eye Infections/virology , Humans , Keratitis/epidemiology , Keratitis/etiology , Keratitis/microbiology , Keratitis/physiopathology , Lipids/chemistry , Retrospective Studies
13.
Cornea ; 38(8): 951-954, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31276458

ABSTRACT

PURPOSE: To describe the outcomes of tuck-in tenon patch graft (TPG) in the management of corneal perforation up to 5-mm size. METHODS: Thirty-one cases of sterile corneal perforation (3-5 mm) underwent autologous TPG. The technique included, freshening of the edges, measuring the size of defect, creating a 360-degree stromal pocket around the perforation margin, harvesting the tenon graft followed by tucking into the stromal pocket, and application of cyanoacrylate glue or suturing the graft using 10-0 monofilament nylon suture. The main outcome measure was rate of healing (percentage of cases healed). RESULTS: The mean age was 52.3 ± 8.9 years with 22 male and 9 female patients. The various etiologies of corneal perforation included trauma (n = 10), neurotrophic keratitis (n = 11), and peripheral ulcerative keratitis (n = 10). The mean size of corneal perforation was 4.2 ± 0.6 mm (range 3-5 mm). The mean duration of epithelial healing was 25.7 ± 6.7 days. Best-corrected visual acuity improved from 1.8 ± 0.4 to 1.2 ± 0.4 logarithm of the minimum angle of resolution units at 4 weeks after surgery (P ≤ 0.01). Twenty-seven (87.1%) cases healed with formation of a leucomatous scar at 16.9 ± 2.7 weeks, whereas 4 cases had a flat anterior chamber. In three-fourths of the cases, a corneal graft was performed. In one case, graft resuturing was performed for post-op aqueous leak, which healed with the formation of a corneo-iridic scar. CONCLUSIONS: TPG is a safe, simple, inexpensive, and an effective technique for the management of corneal perforations. The advantages include the autologous nature of the graft, cost effectiveness, and easy availability.


Subject(s)
Corneal Perforation/surgery , Corneal Ulcer/surgery , Tenon Capsule/transplantation , Adult , Aged , Corneal Perforation/physiopathology , Corneal Ulcer/physiopathology , Cyanoacrylates/therapeutic use , Female , Humans , Male , Middle Aged , Retrospective Studies , Suture Techniques , Tissue Adhesives/therapeutic use , Transplantation, Autologous , Visual Acuity/physiology , Wound Healing/physiology
14.
Cont Lens Anterior Eye ; 42(4): 455-461, 2019 08.
Article in English | MEDLINE | ID: mdl-30808596

ABSTRACT

PURPOSE: To investigate the disease patterns of Microbial Keratitis(MK) in patients seen in a tertiary referral hospital, to evaluate the clinical outcomes of MK and the risk factors for poorer visual outcomes. METHODS: This is a retrospective case series of all culture-positive corneal scrapings between April 2012 and October 2016. A total of 230 patients(n = 230) were included into this study. Patient demographics, clinical information and microbiological characteristics of organisms are collected. RESULTS: 64.3% of patients with MK are contact lens(CL) users. Among CL users, there is a preponderance of females(68.9%) and they tend to be younger (27.1 ± 10.6 years). The most frequently isolated organism in this study is Pseudomonas aeruginosa(51.7%) with 69.6% of cases belonging to CL users. MK in non-CL users tend to involve other organisms, such as coagulase-negative Staphylococci, Staphylococcus aureus and Streptococcus pneumoniae. Pseudomonas aeruginosa exhibits good sensitivity rates to ciprofloxacin, levofloxacin and gentamicin. Non-Pseudomonas organisms display similar sensitivities to ciprofloxacin, levofloxacin and gentamicin. MK in non-CL users is related to predisposing factors of prior ocular trauma and concomitant ocular pathology. They tend to have worse visual acuity(VA) on presentation and after treatment compared to CL users. Poorer VA outcome is associated with larger ulcers, increasing age, trauma and non-CL wearers. Successful clinical outcome is achieved in 97.8% of patients, with only 2.2% requiring further surgical intervention. CONCLUSION: CL use alters the disease patterns of MK as well as the underlying microbiological etiology. Fluoroquinolones and aminoglycosides are good empirical antibiotics for MK treatment. Early referral to a tertiary centre will likely allow for earlier treatment, which can result in better VA outcome, especially so in patients who are older, non-CL wearers and have larger ulcers with associated trauma.


Subject(s)
Corneal Ulcer/epidemiology , Eye Infections, Bacterial/epidemiology , Adolescent , Adult , Anti-Bacterial Agents/therapeutic use , Bacteria/isolation & purification , Contact Lenses/adverse effects , Corneal Ulcer/drug therapy , Corneal Ulcer/microbiology , Corneal Ulcer/physiopathology , Eye Infections, Bacterial/drug therapy , Eye Infections, Bacterial/microbiology , Eye Infections, Bacterial/physiopathology , Female , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Retrospective Studies , Risk Factors , Singapore/epidemiology , Tertiary Care Centers , Visual Acuity/physiology , Young Adult
16.
Eye Contact Lens ; 44 Suppl 2: S433-S441, 2018 Nov.
Article in English | MEDLINE | ID: mdl-29944500

ABSTRACT

PURPOSE: To report the indications, outcomes, and complications of therapeutic penetrating keratoplasty (Th PK) in patients with corneal perforation and/or nonhealing corneal ulceration. METHODS: A retrospective review was conducted of 51 eyes of 51 patients undergoing Th PK between January 1, 2006 and April 15, 2016. Data collected included patient demographics, visual acuity (VA), size of the corneal infiltrate and epithelial defect, degree of corneal thinning/perforation, microbiological results, surgical details, and postoperative complications. RESULTS: The average age at presentation was 56.0 years (range 6-92 years), and most of the patients were females (n=31, 60.8%). Th PK was performed for corneal perforation in 28 eyes (54.9% of cases), nonhealing corneal ulcer in 16 eyes (31.4% of cases), and imminent risk of corneal perforation in 7 eyes (13.7% of cases). Infection was the most common reason for performing a Th PK and was present in 92.3% (47/51) of all cases. Of the infectious cases, the most common etiologies were bacterial (44.7%, 21/47) and fungal (31.9%, 15/47). The most common identifiable risk factor for undergoing a Th PK was a history of contact lens wear, which was seen in 32.7% of patients. Initial anatomic success was achieved in all patients after performing Th PK. Most patients (33/51; 64.7%) had clear grafts at their last follow-up examination. There was an improvement in VA in 70.2% (33/47, where data were available) of the patients at the final postoperative visit compared with the preoperative visit. Average best postoperative VA (1.14±0.88 logarithm of the minimum angle of resolution [LogMAR]; 20/276) was significantly better than the presenting (1.98±0.68 LogMAR; 20/1910) and preoperative (2.18±0.55 LogMAR; 20/3,027) visual acuities (P<0.0001). The most common complication after Th PK was cataract, which was present in 81.8% (27/33) of phakic eyes in which lens status could be assessed, followed by graft failure (47.1%; 24/51), and secondary glaucoma (45.1%; 23/51). Five eyes developed infection in the therapeutic graft, four eyes had persistent corneal epithelial defect at their last follow-up visit, and two eyes underwent evisceration. CONCLUSIONS: Therapeutic penetrating keratoplasty achieves anatomic success and it is a useful procedure for restoring a stable cornea in cases in which infection fails to heal or when the cornea perforates. Furthermore, Th PK achieves corneal clarity and improves vision in most patients.


Subject(s)
Corneal Perforation/surgery , Corneal Ulcer/surgery , Keratoplasty, Penetrating , Adolescent , Adult , Aged , Aged, 80 and over , Child , Cornea/pathology , Corneal Perforation/physiopathology , Corneal Ulcer/physiopathology , Female , Humans , Male , Middle Aged , Postoperative Complications , Retrospective Studies , Visual Acuity/physiology , Young Adult
17.
Curr Opin Ophthalmol ; 29(4): 373-377, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29708927

ABSTRACT

PURPOSE OF REVIEW: Cytomegalovirus (CMV) keratitis, albeit an uncommon manifestation of this ubiquitous pathogen, can lead to devastating ocular morbidity. Timely diagnosis and appropriate treatment are also unfortunately uncommon. The purpose of this review is to discuss recently published literature regarding the epidemiology, pathophysiology, diagnosis, and therapy of CMV keratitis. RECENT FINDINGS: Classic clinical presentations of CMV keratitis are known; however, current investigations further elucidate characteristics of typical versus atypical disease. Ongoing research stems beyond utilizing PCR analysis towards targeted diagnostic studies with advanced imaging modalities as well as modern genotyping techniques. Strong clinical acumen combined with appropriate handling of these modern technologies are proving invaluable for rapid diagnosis and treatment of this virulent pathogen. SUMMARY: The current recommended treatment for CMV keratitis is systemic ganciclovir. Astute clinicians must consider this diagnosis in any patient with keratitis, anterior uveitis, and intraocular hypertension. Novel diagnostic techniques should be combined with clinical exam findings to accurately and efficiently diagnose, treat, and monitor progression.


Subject(s)
Corneal Ulcer , Cytomegalovirus Infections , Eye Infections, Viral , Antiviral Agents/therapeutic use , Corneal Ulcer/diagnosis , Corneal Ulcer/drug therapy , Corneal Ulcer/epidemiology , Corneal Ulcer/physiopathology , Cytomegalovirus/pathogenicity , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/epidemiology , Cytomegalovirus Infections/physiopathology , Eye Infections, Viral/diagnosis , Eye Infections, Viral/drug therapy , Eye Infections, Viral/epidemiology , Eye Infections, Viral/physiopathology , Ganciclovir/therapeutic use , Humans , Uveitis, Anterior/diagnosis
18.
J Cataract Refract Surg ; 44(2): 245-247, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29587979

ABSTRACT

Autologous tissue from correction of myopia with small-incision lenticule extraction in 1 eye of a patient was used to enhance corneal curvature in the contralateral eye, in which a corneal ulcer had flattened the cornea. Regularization of the corneal tomography was achieved, improving the visual quality and visual capacity of the patient.


Subject(s)
Corneal Stroma/surgery , Corneal Stroma/transplantation , Corneal Surgery, Laser/methods , Corneal Transplantation/methods , Corneal Ulcer/surgery , Myopia/surgery , Transplantation, Autologous , Adult , Autografts , Corneal Pachymetry , Corneal Topography , Corneal Ulcer/physiopathology , Female , Follow-Up Studies , Humans , Myopia/physiopathology , Refraction, Ocular/physiology , Visual Acuity/physiology
19.
Cornea ; 37(2): 260-262, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29309359

ABSTRACT

PURPOSE: To report a case of extensive Fuchs superficial marginal keratitis managed with annular lamellar keratoplasty. METHODS: Interventional case report. RESULTS: A 72-year-old man presented with 20/80 best-corrected visual acuity in his left eye and demonstrated 360-degree peripheral deep immune stromal keratitis and pseudopterygia with peripheral stromal thinning. During superficial keratectomy with amniotic membrane transplantation, the thin cornea was perforated while excising pseudopterygia in the superonasal quadrant. Surgery was aborted. Anterior segment optical coherence tomography demonstrated a severely thinned cornea (240 µm nasally, 360 µm temporally) with overlying pseudopterygia peripherally. After allowing 3 months for the cornea to heal, the decision was made to perform lamellar annular (or "donut") keratoplasty. The patient had an unremarkable postoperative course, with 20/50 best-corrected visual acuity 10 months after keratoplasty. CONCLUSIONS: We report an extensive case of Fuchs superficial marginal keratitis treated with 360-degree annular lamellar keratoplasty. This technique provides tectonic support to decrease the likelihood of future perforation while also improving vision by modifying the ectatic cornea. Anterior segment optical coherence tomography may be a helpful tool preoperatively to avoid severely thinned areas (eg, during pseduopterygium removal) and to ensure complete removal of the ectatic cornea.


Subject(s)
Corneal Transplantation , Corneal Ulcer/surgery , Aged , Corneal Pachymetry , Corneal Topography , Corneal Ulcer/physiopathology , Humans , Male , Tomography, Optical Coherence , Visual Acuity/physiology
20.
J Fr Ophtalmol ; 41(1): 57-61, 2018 Jan.
Article in French | MEDLINE | ID: mdl-29305170

ABSTRACT

PURPOSE: To determine the frequency of corneal ulcer in our practice environment. METHODOLOGY: This study was conducted at Saint-Joseph Hospital in Kinshasa and at the Lubumbashi University Clinics in the Democratic Republic of Congo from January 2011 to December 2014. We studied the frequency, demographic and clinical variables of corneal ulcer patients. RESULTS: A total of 380 cases of corneal ulcers were recorded out of 44,722 ophthalmologic consultations performed, with a frequency of 0.85% and a sex ratio ranging from 1.4 to 1.7 men to women. Corneal ulcer was diagnosed in patients of all ages; the mean age was 38.67±18.67 years. Patients with corneal ulcers presented for eye pain (80%), followed by tearing, photophobia, eye redness and blurred vision. The frequency of visual impairment was 10.30%; 2.1% of patients had vision reduced to light perception, and 1% of patients had no light perception. Corneal dystrophy was present in 41.6% of cases. Perforation of the globe and endophthalmitis were observed in 3.4% of cases each. CONCLUSION: Corneal ulceration is one of the leading causes of visual impairment and blindness in our practice environment. An early ophthalmologic consultation at the onset of symptoms and adequate management would improve the visual prognosis of patients.


Subject(s)
Corneal Ulcer/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Corneal Ulcer/complications , Corneal Ulcer/physiopathology , Democratic Republic of the Congo/epidemiology , Female , Humans , Infant , Male , Middle Aged , Prevalence , Retrospective Studies , Vision Disorders/epidemiology , Vision Disorders/etiology , Visual Acuity , Young Adult
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