Characteristics of Hyaluronic Acid and Its Use in Ocular Surface Diseases Including Dry Eye

Hyaluronic acid (HA) is a polysaccharide found in the extracellular matrix of the epithelial, nervous, and connective tissues of vertebrates. It is widely used in the treatment of ocular surface diseases (OSDs), including dry eye, due to its high water-retaining capacity, viscoelasticity, and role as a signaling molecule in inflammation and wound healing. This paper reviews the physicochemical and biological properties of HA related to the treatment of OSDs and the results of published preclinical studies, clinical trials, and meta-analyses on the effects of HA eye drops on the tear film, the mechanism of action of HA eye drops, and its clinical effects and adverse events in OSDs, such as corneal/conjunctival epithelial defects, dry eye, and postoperative dry eye. This review should help inform clinical judgments by providing clinical evidence and precautions on the use of HA eye drops in OSDs, including dry eye.

The Status of Infectious Keratitis in Gwang-ju, Jeonnam, Republic of Korea

Purpose@#To investigate the clinical characteristics of infectious keratitis in Gwang-ju, Jeonnam Province, Korea. @*Methods@#We retrospectively reviewed the medical records of 260 eyes of 260 patients diagnosed with infectious keratitis at the Chosun University Hospital from January 2015 to February 2020. @*Results@#The mean age of disease onset was 58.9 years; 132 (50.8%) of all patients were male and 128 (49.2%) female. The culture positivity rate was 24.6%. Gram-negative bacteria were cultured from 38 eyes (59%), Gram-positive bacteria from 21 (33%), and fungi from five (8%). The most commonly isolated microorganism was Stenotrophomonas (xanthomonas) maltophilia (a Gram-negative rod; 17 cases [26.6%]). Prior use of topical antibiotics was significantly more prevalent in the culture-negative than -positive group. In the latter group, the initial visual acuity was poor (p = 0.015) and the frequency of epithelial defects ≥5 mm2 in area was higher than in the culture-negative group (p = 0.001). Trauma caused by vegetable matter (44 eyes, 16.9%) was the most common predisposing factor. The risk factors for a poor visual outcome were such trauma (p = 0.013), previous ocular surgery (p = 0.006), an epithelial defect area greater than 5 mm2 (p < 0.001), and a follow-up period <10 months (p = 0.005). @*Conclusions@#The Gwangju Jeollanam-do community is more rural than urban, contains a large older population, and features few hospitals. Staphylococcus epidermidis and Pseudomonas aeruginosa are considered to be the most frequent causes of infectious keratitis in Korea. However, in our study Stenotrophomonas maltophilia was the organism most frequently cultured.

The Effect of Topical 10% N-acetylcysteine on Refractory Filamentary Keratitis

PURPOSE@#To analyze the effects of topical 10% N-acetylcysteine on patients with refractory filamentary keratitis.@*METHODS@#The present study included 29 eyes from 20 patients diagnosed with filamentary keratitis. We analyzed the cause of filamentary keratitis, types of treatments, symptom scores, number of filaments, fluorescein staining, degrees of remission, and recurrence of the disease.@*RESULTS@#A total of 19 eyes treated with filament removal, therapeutic contact lenses, topical antibiotics, topical steroids, topical 0.05% cyclosporine, artificial tears, and punctal plugs showed improvements. Topical 10% N-acetylcysteine was added to 10 patients who did not respond to the usual treatment for more than 1 month. Seven eyes showed a complete remission of disease at an average of 56.22 ± 24.52 days. Two eyes showed a partial remission with less than 1–2 fillaments. One eye stopped 10% N-acetylcysteine treatment because of an irritable sensation.@*CONCLUSIONS@#Topical 10% N-acetylcysteine was an effective treatment for refractory filamentary keratitis.

Primary Amyloidosis Localized to the Conjunctiva

PURPOSE: To report a case of primary amyloidosis localized to the conjunctiva. CASE SUMMARY: A 19-year-old male with a conjunctival mass and foreign body sensations in the right eye transferred from another hospital. A 0.5 × 2.5 cm reddish mass was present in the medial canthus of the right conjunctiva with no other clinically specific signs. Surgical excisional biopsy was performed. Histological examination showed amyloid deposition. There was no other orbital involvement apart from the conjunctiva. Abnormalities were not found in the systemic examination. CONCLUSIONS: We report a case of primary amyloidosis localized to the conjunctiva.

A Case of Acute Interstitial Keratitis in a Patient with Acquired Syphilis

PURPOSE: To report a case of acute interstitial keratitis as the first clinical sign in a patient with latent syphilis. CASE SUMMARY: A 23-year-old female presented with visual impairment and discomfort in her right eye that developed 3 days earlier. The visual acuity in the right eye was 20/200 and corrected to 20/100, and slit lamp examination showed round sub-epithelial opacification in the central cornea with stromal edema and neovascularization on the cornea of the right eye. Whole body tests including serological tests were performed. Under the suspicion of acute interstitial keratitis, topical antibiotics and steroids were applied 4 times a day initially. Serological tests were reactive for venereal disease research laboratory test (VDRL). Under the suspicion of acute interstitial keratitis due to syphilis, fluorescent treponemal antibody absorption test IgM/IgG (FTA-ABS IgM/IgG) was performed; a positive result for FTA-ABS IgG led to diagnosis of acute interstitial keratitis with latent syphilis. During treatment, systemic doxycycline 200 mg for 4 weeks with topical antibiotics and steroids were administered, the opacity and edema of the cornea regressed after 2 weeks of treatment, and visual acuity in the patient's right eye improved to 20/20. CONCLUSIONS: We report an unusual case of acute interstitial keratitis as the first clinical manifestation of latent syphilis in an immunocompetent patient.

Cryotherapy on Refractory Fungal Corneal Ulcer: A Case Report

PURPOSE: We report a case of cryotherapy for fungal corneal ulcers that did not respond to antifungal agents. CASE SUMMARY: A 58-year-old man was transferred to our hospital with a left eye corneal ulcer due to pain and visual impairment in his left eye for two weeks, and he was suspected to have a history of fungal infection. At the time of admission, corneal opacity and progressive ulcerative lesions were observed at 5 o'clock in the left eye and visual acuity was 0.025, uncorrected. The corneal ulcer marginal resection, bacterial culture, and potassium hydroxide preparation (KOH) test were performed on lesion sites. Cultures of Candida albicans were reported to grow, topical antibiotics (Fortified tobramycin, Fortified cefazolin, moxifloxacin), and anti-fungal agents (fortified amphotericin B, 0.5%, Natamycin) were administered, but no improvement was observed for 2 weeks. On the 14th day after admission, Cryotherapy was performed. After surgery, eye drops were equally applied, and there was no other discomfort other than pain for 3 days after the operation. He discharged 10 days after surgery, the corneal lesion was healed and the visual acuity was improved to 0.32, uncorrected. CONCLUSIONS: We report a case of cryotherapy for fungal corneal ulcers that did not react with topical antifungal drugs and improved visual acuity and symptom improvement.

Choroidal Blood Flow Change in Eyes with High Myopia

PURPOSE: To evaluate choroidal blood flow changes in eyes with high myopia according to the pulsatile components of ocular blood flow analysis. METHODS: A total of 104 subjects (52 males and 52 females) were included in this study. One eye of each participant was randomly selected and assigned to one of four refractive groups, designated as, hyperopes (n = 20; refractive error, > or =+1.00 diopter [D]), emmetropes (n = 28; refractive error, +/-0.75 D), lower myopes (n = 33; refractive error, -1.00 to -4.75 D), and high myopes (n = 23; refractive error, < or =-5.00 D). Components of pulse amplitude (OBFa), pulse volume (OBFv), pulse rate (OBFr), and pulsatile ocular blood flow (POBF) were analyzed using a blood flow analyzer. Intraocular pressure and axial length were measured. RESULTS: Pulsatile components of OBFa, OBFv, and POBF showed positive correlations with refractive error and showed negative correlations with axial length (r = 0.729, r = 0.772, r = 0.781, respectively, all p < 0.001; r = -0.727, r = -0.762, r = -0.771, respectively, all p < 0.001). The correlations of refractive error and axial length with OBFr were irrelevant (r = -0.157, p = 0.113; r = 0.123, p = 0.213). High myopes showed significantly lower OBFa, OBFv, and POBF than the other groups (all p < 0.001). CONCLUSIONS: Axial length changes in high myopes potentially influence choroidal blood flow, assuming the changes are caused by narrowing of the choroidal vessel diameter and increasing rigidity of the choroidal vessel wall. These finding explains the influence of axial length on OBFa, OBFv, and POBF, but not on OBFr. Thus, changes in axial length and the possible influence of these changes on the physical properties of choroidal vessels is the mechanism believed to be responsible for putting high myopes at risk for ocular vascular diseases.

Comparative Quantification of Plasma TDRD7 mRNA in Cataract Patients by Real-time Polymerase Chain Reaction

PURPOSE: To investigate the relationship between plasma TDRD7 mRNA and lens transparency, and to evaluate plasma TDRD7 mRNA as a potential marker for cataracts and its sub-type by quantitatively analyzing human peripheral blood. METHODS: Plasma RNA was extracted from 40 patients with cataracts, and 30 normal controls of matched age and gender. Blood cholesterol and fasting glucose were measured, and the RNA extracted from the sample was synthesized into cDNA. After polymerase chain reaction, the results were compared after quantifying the TDRD7 mRNA using ABL1 mRNA for normalization. We analyzed the relative gene expression data via the DeltaDeltaCt method. RESULTS: The normalized 2(-DeltaDeltaCt) of plasma TDRD7 mRNA based on ABL1 mRNA was 1.52 ± 0.63 in the case of the control group and 1.05 ± 0.34 in the case of the cataract patients, and the TDRD7 expression level of the cataract patients was lower than that of the control group (p = 0.048). The comparison of the genetic values of different types of cataracts demonstrated that the TDRD7 expression level of the cortical type and mixed type were lower than those of the nuclear type and posterior subcapsular opacity type (p = 0.017). CONCLUSIONS: Human cataracts and the TDRD7 gene loss-of-function mutations are strongly causally related, as the expression level of plasma TDRD7 mRNA in patients with cataracts was statistically significantly lower than in the normal control group.

Evaluation of the Stabilization of Human Umbilical Cord Blood-Derived Mast Cells in Accordance with Ketotifen and Olopatadine Concentration

PURPOSE: To evaluate the effect of olopatadine and ketotifen to stabilize mast cells using human umbilical cord blood-derived mast cells (hCBMCs). METHODS: Using cultured hCBMCs, we divided the cells into the Ketotifen fumarate treatment group, the Olopatadine hydrochloride treatment group, the positive control group, and the negative control group. The histamine release inhibition rate was then observed. RESULTS: Ketotifen and olopatadine both showed the highest inhibition rate of histamine release at a concentration of 10(-3.5)M (Ketotifen, 48% and Olopatadine, 62%). The histamine release inhibition rate of olopatadine was 28% at a concentration of 10(-5.5)M, but ketotifen demonstrated a low histamine release inhibition rate at the same concentration. Ketotifen and olopatadine showed no histamine release inhibition at concentrations of 10(-2)~10(-2.5)M, and 10(-6)M. CONCLUSIONS: Ketotifen and olopatadine demonstrated histamine inhibition in the concentration range of 10(-3) to 10(-5)M. Olopatadine showed a slightly stronger response than ketotifen in the inhibition of histamine release.

Utility of the Noncontact Specular Microscopy for Measurements of Central Corneal Thickness

PURPOSE: To evaluate the efficacy of noncontact specular microscopy (NCSM) by comparing the measurement of central corneal thickness (CCT) to the measurement with anterior segment optical coherence tomography (AS-OCT) and ultrasound pachymetry (USP). METHODS: One examiner measured the CCT of 50 eyes of 50 healthy young subjects using NCSM, AS-OCT, and USP. The mean values and correlations were analyzed. RESULTS: The mean CCT value was 546.92 +/- 32.06 microm with NCSM, 535.24 +/- 30.54 microm with AS-OCT, and 546.38 +/- 30.70 microm with USP. The CCT measurements with NCSM and USP were significantly thicker than with AS-OCT (p 0.900 in all groups, p < 0.001 in all groups). CONCLUSIONS: CCT measurements of healthy eyes using NCSM are more correlated with USP than AS-OCT. The CCT measurement using NCSM is a better alternative for USP than AS-OCT.

Keratitis with Elizabethkingia meningoseptica Occurring after Contact Lens Wear: A Case Report

To report keratitis with Elizabethkingia meningoseptica, which occurred in a healthy patient after wearing contact lenses for 6 months. A 24-year-old male patient visited our hospital with ocular pain. This patient had a history of wearing soft contact lenses for 6 months, about 10 hours per day. At initial presentation, slit lamp examination showed corneal stromal infiltrations and small epithelial defect. Microbiological examinations were performed from corneal scrapings, contact lenses, and the contact lens case and solution. The culture results from contact lenses, contact lens case and solution were all positive for Elizabethkingia meningoseptica. Thus, we could confirm that the direct cause of keratitis was contamination of the contact lenses. The patient was treated with 0.3% gatifloxacin. After treatment, the corneal epithelial defect was completely healed, and a slight residual subepithelial corneal opacity was observed. We diagnosed keratitis with Elizabethkingia meningoseptica in a healthy young male wearing soft contact lenses. We conclude that Elizabethkingia meningoseptica should be considered as a rare but potential pathogen for lens-related keratitis in a healthy host.

Keratitis with Elizabethkingia meningoseptica Occurring after Contact Lens Wear: A Case Report

To report keratitis with Elizabethkingia meningoseptica, which occurred in a healthy patient after wearing contact lenses for 6 months. A 24-year-old male patient visited our hospital with ocular pain. This patient had a history of wearing soft contact lenses for 6 months, about 10 hours per day. At initial presentation, slit lamp examination showed corneal stromal infiltrations and small epithelial defect. Microbiological examinations were performed from corneal scrapings, contact lenses, and the contact lens case and solution. The culture results from contact lenses, contact lens case and solution were all positive for Elizabethkingia meningoseptica. Thus, we could confirm that the direct cause of keratitis was contamination of the contact lenses. The patient was treated with 0.3% gatifloxacin. After treatment, the corneal epithelial defect was completely healed, and a slight residual subepithelial corneal opacity was observed. We diagnosed keratitis with Elizabethkingia meningoseptica in a healthy young male wearing soft contact lenses. We conclude that Elizabethkingia meningoseptica should be considered as a rare but potential pathogen for lens-related keratitis in a healthy host.

Achromobacter xylosoxidans Keratitis after Contact Lens Usage

To report on Achromobacter xylosoxidans keratitis in two healthy patients who had worn contact lenses foran extended period of time. A 36-year-old female and a 21-year-old female visited our hospital with ocular pain and blurred vision. Both patients had a history of wearing soft contact lenses for over fve years with occasional overnight wear. At the initial presentation, a slit lamp examination revealed corneal stromal infiltrations and epithelial defects with peripheral neovascularization in both patients. Microbiological examinations were performed from samples of corneal scrapings, contact lenses, contact lens cases, and solution. The culture resulting from the samples taken from the contact lenses, contact lens cases, and solution were all positive for Achromobacter xylosoxidans. Confrming that the direct cause of the keratitis was the contact lenses, the frst patient was prescribed ceftazidime and amikacin drops sensitive to Achromobacter xylosoxidans. The second patient was treated with 0.3% gatifoxacin and fortifed tobramycin drops. After treatment, the corneal epithelial defects were completely healed, and subepithelial corneal opacity was observed. Two cases of Achromobacter xylosoxidans keratitis were reported in healthy young females who wore soft contact lenses. Achromobacter xylosoxidans should be considered a rare but potentially harmful pathogen for lens-induced keratitis in healthy hosts.

Clinical Results of Modified Ab Externo and One-Knot Technique

PURPOSE: To introduce a more efficient and time-saving scleral fixation technique for a posterior chamber foldable intraocular lens and to report the clinical results. METHODS: A foldable acrylic 3-Piece IOL was sutured to the sclera via a small corneal incision. The guiding hollow needle was not used, which differs from other ab externo techniques. Instead, the curved long needle was directly pulled out through the cornea. The scleral flap was not used to bury the scleral suture knot; Instead, the scleral suture knot was translocated at the temporal area. RESULTS: A total of 30 cases were studied retrospectively. The mean follow-up period was 2 years. The IOL was correctly positioned in all cases. There were no major complications, such as endophthalmitis or suture erosion through the conjunctiva. CONCLUSIONS: Based on the authors' experience, the modified ab externo and one-knot technique is a faster and easier technique than the conventional ab externo technique.

Clinical Results of Modified Ab Externo and One-Knot Technique

PURPOSE: To introduce a more efficient and time-saving scleral fixation technique for a posterior chamber foldable intraocular lens and to report the clinical results. METHODS: A foldable acrylic 3-Piece IOL was sutured to the sclera via a small corneal incision. The guiding hollow needle was not used, which differs from other ab externo techniques. Instead, the curved long needle was directly pulled out through the cornea. The scleral flap was not used to bury the scleral suture knot; Instead, the scleral suture knot was translocated at the temporal area. RESULTS: A total of 30 cases were studied retrospectively. The mean follow-up period was 2 years. The IOL was correctly positioned in all cases. There were no major complications, such as endophthalmitis or suture erosion through the conjunctiva. CONCLUSIONS: Based on the authors' experience, the modified ab externo and one-knot technique is a faster and easier technique than the conventional ab externo technique.

A Statistical Observation of Corneal Laceration and Factors Influencing Visual Prognosis

PURPOSE: To investigate the regional characteristics and the factors that influence final visual acuity in corneal laceration and use the results for prevention and treatment of corneal laceration. METHODS: Sixty-eight patients who visited the Chosun University Medical Center from January 1, 2006 to December 31, 2010 were retrospectively surveyed. The incidence of corneal laceration, sex, age, monthly and seasonal distribution, cause, site and length of corneal laceration, secondary operation, complications, and ocular trauma score were reviewed statistically. In additional, the factors influencing visual prognosis were investigated. RESULTS: The incidence was more common in males (94.1%) and in the 6th-decade of life (29.4%). The corneal laceration was more common in the summer (38.2%) and in September (26.5%) and the most common cause was stone (39.7%) and metal (35.3%), respectively. The corneal laceration tended to occur at the corneal center. The most common first operation was primary closure (81.9%), and the secondary operation was most often performed due to a traumatic cataract (32.1%). The factors that significantly influenced the final visual acuity were initial visual acuity, length and site of laceration, and secondary operation. CONCLUSIONS: The present survey investigated the regional characteristics and important factors influencing final visual acuity. Results show initial visual acuity, the length and site of laceration, and the secondary operation significantly influenced final visual acuity.

Mechanisms of Apoptosis on Human Lens Epithelium after Ultraviolet Light Exposure

PURPOSE: The purpose of this study is to understand the mechanism of apoptosis occurring on a cultured human lens epithelial cell line after exposure to ultraviolet (UV) light. We intended to confirm the presence of cellular toxicity and apoptosis and to reveal the roles of p53, caspase 3 and NOXA in these processes. METHODS: Cells were irradiated with an ultraviolet lamp. Cellular toxicity was measured by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Hoechst staining and fluorescent anti-caspase 3 antibodies were used for apoptosis investigation. The quantities of p53, caspase 3, and NOXA were measured by Western blotting for to investigate the apoptosis pathway. RESULTS: Cellular toxicity on the human lens epithelium markedly increased with time after UV exposure. On Hoechst staining, we found that apoptosis also remarkably increased after exposure to ultraviolet light, compared with a control group. In the immunochemical study using anti-caspase 3 antibodies, active caspase 3 significantly increased after exposure to ultraviolet light. On Western blotting, p53 decreased, while caspase 3 and NOXA increased. CONCLUSIONS: Exposure of cultured human lens epithelial cell lines to ultraviolet light induces apoptosis, which promotes the expression of NOXA and caspase 3 increases without increasing p53. This may suggest that UV induced apoptosis is caused by a p53-independent pathway in human lens epithelial cells.

Keratoconjunctival Chemical Burn due to Chemical Light

PURPOSE: Chemical lights, also called Luminous Sticks, consist of a solution of diphenyl oxalate (C14H10O4) and hydrogen peroxide (H2O2). Human tissue can be damaged when the mixed solution contacts the human body. The authors report a single case of chemical injury of keratoconjunctiva by exposure to chemical lights. CASE SUMMARY: A 47-year-old man's right eye accidentally contacted the fluorescent material when breaking a Luminous Stick 7 days before being referred to our clinic. He had pain in the right eye and experienced visual loss. The patient's best corrected visual acuity in the right eye was 20/50. An ulcerative lesion with edema at the inferior bulbar and palpebral conjunctiva and coneal epithelial defect was observed upon biomicroscopic examination. The patient was hospitalized and antibiotics, steroids, mydriatic and artificial tear eye drops were applied for treatment. After 9 days of treatment, the best corrected visual acuity of the patient recovered to 20/20, and the conjunctiva and cornea were mostly healed. No complication was observed. CONCLUSIONS: Chemical lights are commonly used in concerts and festivals. If the contents contact the eyes when breaking he chemical lights, various chemical burns can occur and cause ophthalmologic complications. Since no regulations have been passed regarding chemical lights, safety education and supervision are considered to be necessary for children.

Methotrimeprazine-induced Corneal Deposits and Cataract Revealed by Urine Drug Profiling Test

Two schizophrenic patients who had been taking medication for a long period presented with visual disturbance of 6-month duration. Slit-lamp examination revealed fine, discrete, and brownish deposits on the posterior cornea. In addition, bilateral star-shaped anterior subcapsular lens opacities, which were dense, dust-like granular deposits, were noted. Although we strongly suspected that the patient might have taken one of the drugs of the phenothiazine family, we were unable to obtain a history of medications other than haloperidol and risperidone, which were taken for 3 yr. We performed a drug profiling test using urine samples and detected methotrimeprazine. The patient underwent surgery for anterior subcapsular lens opacities. Visual acuity improved in both eyes, but the corneal deposits remained. We report an unusual case of methotrimeprazine-induced corneal deposits and cataract in a patient with psychosis, identified by using the urine drug profiling test.

Various Treatments Using Invaluable Donor Cornea

PURPOSE: To report cases of transplanting a donor's 2 corneas to 5 patients suffering from several corneal diseases. CASE SUMMARY: Two corneas were donated from a 66-year-old donor, who suffered from brain damage due to asphyxia, one hour after being pronounced dead by doctors. Two penetrating keratoplasties and 3 partial lamellar keratoplasties were performed for patients with corneal opacity, corneal ulcer and corneal perforation. After the procedure all grafts were stable. CONCLUSIONS: Under the present circumstances of decreasing donations of corneas after death and the increasing demand for keratoplasty in Korea, the mutual cooperation among hospitals to treat more than one patient using one donated cornea is a method the authors believe can alleviate this situation.