VOLUME 82 - ISSUE 1

Purpose: To determine whether a correlation exists between pathogenic species and clinical findings, disease severity, and visual outcome in patients with keratitis and fungal growth in microbiological culture.
Methods: A retrospective study of patients with fungal growth in the microbiological culture of corneal scrapings. Patients were treated at an ophthalmologic reference center in Southeastern Brazil from January 1992 to October 2015.
Results: Medical records of 181 patients (131 males and 50 females) with a mean age of 47 ± 18 years were analyzed. The three most common etiologies were Fusarium sp. (38.7%), Aspergillus sp. (15%), and Candida sp. (13.2%). Among these, Fusarium sp. was the most frequent in patients aged ≤50 years (p=0.002) and in those with a recent history of a foreign body and/or ocular trauma (p=0.01). Candida sp. was the most frequent etiology in patients aged >50 years (p=0.002), in those with postoperative ocular surgery (p=0.002); in those with a previous ocular pathology (p=0.0007); and in immunodepressed patients (p=0.0004).
Conclusion: Fusarium sp. was predominant in patients aged ≤50 years and those with a recent history of foreign body and/or ocular trauma, whereas Candida sp. was predominant in older adults, in those with a postoperative ocular surgery, in those with a previous ocular pathology, and in immunodepressed patients.

Keywords: Keratitis; Eye infections, fungal; Corneal ulcer; Risk factors

Purpose: Obesity is associated with eye diseases, but the underlying structural changes and pathogenic mechanisms have not been examined in detail. Here, we assessed the effects of morbid obesity on the morphometric indices of eye disease.
Methods: Morbidly obese volunteers (n=101, body mass index [BMI] ≥40) and healthy individuals (n=95, BMI: 18.50-24.99) were examined by Goldman applanation tonometry, pachymetry, and spectral domain optical coherence tomography. Intraocular pressure, anterior chamber depth, axial length, central corneal thickness, retinal nerve fiber layer thickness, central foveal thickness, and choroidal thickness were compared between groups.
Results: Uncorrected intraocular pressure was significantly greater in the morbidly obese group than in the healthy control group (15.5 ± 2.5 vs. 14.5 ± 2.6 mmHg, p=0.009), whereas axial length, anterior chamber depth, and central corneal thickness did not differ between the groups. The mean retinal nerve fiber layer thickness at the temporal quadrant was reduced in the morbidly obese group (72.7 ± 13.6 vs. 85.05 ± 52.6 µm, p=0.024). Similarly, the mean retinal thicknesses at nasal and temporal 1500-µm locations were lower in the morbidly obese group (346.6 ± 18.2 vs. 353.7 ± 18.8 µm, p=0.008; 323.1 ± 20.3 vs. 330.0 ± 18.9 µm, p=0.001). The mean choroidal thickness was also reduced in almost all measurement locations (fovea, temporal 500 and 1000 µm, and nasal 500, 1000, and 1500 µm) of the obese group (p<0.05). Weight and BMI were negatively correlated with subfoveal choroidal thickness (r=-0.186, p=0.009; r=-0.173, p=0.015).
Conclusion: Morbid obesity is associated with elevated uncorrected intraocular pressure and signs of neuropathy and retinopathy. Obesity may thus increase the risks of glaucoma and glaucomatous optic neuropathy.

Keywords: Morbid obesity; Intraocular pressure; Nerve fibers; Corneal pachymetry; Anterior eye segment; Posterior eye segment

Purpose: To investigate the frequency of toxic retinopathy in patients with lupus erythematosus and rheumatoid arthritis with long-term use of chloroquine diphosphate or hydroxychloroquine through spectral domain optical coherence tomography and the outcomes of ophthalmological exams (visual acuity - Snellen’s table, color vision test - Ishihara’s table, fundoscopy, and retinography - red-free).
Methods: A cross-sectional study was carried out involving the ophthalmologic evaluation of patients using regular chloroquine diphosphate or hydroxychloroquine for a period of 1 year or longer. The patients completed a questionnaire on their opinions and treatment regularity. The same patients underwent ophthalmologic examination and spectral domain optical coherence tomography.
Results: The prevalence of toxic retinopathy caused by antimalarials was 4.15% (9 of 217 patients), 7.4% (4 of 54 patients) following chloroquine diphosphate usage, and 0.82% (1 of 121 patients) following hydroxychloroquine usage. Only patients with advanced stage maculopathy presented abnormalities during the ophthalmologic exam: the color vision test was altered in 11.1%, and visual acuity and fundoscopy were altered in 33.3%. Identification of early toxic retinopathy, detected in six patients, was possible using spectral domain optical coherence tomography. The mean duration of antimalarial drug usage among patients with toxic retinopathy was 10.4 years. Only 31% of the patients reported some symptoms during treatment, and although 24% were afraid to use the medication, they did so as prescribed.
Conclusion: Use of spectral domain optical coherence tomography was essential for the diagnosis of early-stage antimalarial toxic retinopathy in patients with the following characteristics: asymptomatic, antimalarial use 7 days a week for a period of more than 5 years, and normal clinical ophthalmologic examination.

Keywords: Retinopathy/etiology; Antimalarials/adverse effects; Hydroxychloroquine/adverse effects; Chloroquine/adverse effects; Tomography, optical coherence/methods

Purpose: To evaluate the effect of accelerated corneal crosslinking on corneal biomechanics with an ocular response analyzer in patients with progressive keratoconus.
Methods: In this retrospective study, 50 eyes of 45 patients with progressive keratoconus who underwent accelerated corneal crosslinking were evaluated with ocular response analyzer waveform parameters before and one year after corneal crosslinking. Paired two-tailed Student’s t-test was performed to compare the parameters before vs. after corneal crosslinking.
Results: Mean patient age was 17.6 ± 3.6 (range 9-25) years. A significant increase was observed in p1 area, p2 area, h2, and dive2 values. No significant difference in corneal hysteresis, corneal resistance factor, or other waveform-derived parameters was observed at one year postoperatively.
Conclusion: For estimating the effect of accelerated corneal crosslinking on corneal biomechanics, parameters such as p1 area, p2 area, h2, and dive2 are more sensitive than corneal hysteresis and corneal resistance factor. These results may help us to find out which corneal crosslinking method is most effective for stiffening the cornea.

Keywords: Keratoconus; Cornea/physiopathology; Corneal crosslinking; Corneal hysteresis; Diagnostic techniques, ophthalmological

Purpose: To compare effects of 5% topical povidone iodine with prophylactic topical azithromycin and moxifloxacin on bacterial flora in patients undergoing intravitreal injection.
Methods: A total of 132 patients were randomly assigned to receive treatment with azithromycin or moxifloxacin, or no treatment (control group). In total, 528 specimens were obtained at the time of admission, 4 days before intravitreal injection, 4 days after intravitreal injection, and 8 days after intravitreal injection. Samples were immediately sent to the microbiology laboratory for incubation.
Results: The microorganism observed most frequently was coagulasenegative Staphylococcus (23.8%). When the results of samples obtained on Day 4 before injection were assessed, growth of coagulase-negative Staphylococcus was significantly lower in the moxifloxacin group, compared with controls (p=0.049). Acinetobacter baumannii continued to grow after administration of azithromycin (p=0.033). When the results of four days after intravitreal injection were evaluated, growth of coagulase-negative Staphylococcus was higher in controls, compared with patients who received azithromycin or moxifloxacin (p=0.004). Eradication rate was significantly higher in the moxifloxacin group than in the control group (p=0.001). Samples obtained on Day 8 after intravitreal injection showed similar levels of bacterial growth in all groups (p=0.217).
Conclusion: Moxifloxacin was more effective than 5% povidone iodine in controlling the growth of conjunctival bacterial flora. Use of moxifloxacin in combination with 5% povidone iodine resulted in a synergistic effect.

Keywords: Azithromycin; Conjunctiva/microbiology; Intravitreal injection; Moxifloxacin; Povidone-iodine

Purpose: To evaluate the ability of human immature dental pulp stem cells, which are mesenchymal stem cells of neural crest origin, to differentiate into the corneal epithelium for purposes of corneal transplantation and tissue engineering when cultured on de-epithelized amniotic membranes.
Methods: We compared the immunophenotypes (ABCG2, K3/12, and vimentin) of cells grown on amniotic membranes or plastic surfaces under serum-free conditions or in culture media containing serum or serum replacement components.
Results: Immature dental pulp stem cells grown on amniotic membranes under basal conditions are able to maintain their undifferentiated state. Our data also suggest that the culture medium used in the present work can modulate the expression of immature dental pulp stem cell markers, thus inducing epithelial differentiation of these cells in vitro.
Conclusions: Our results suggest that the amniotic membrane is a good choice for the growth and transplantation of mesenchymal stem cells, particularly immature dental pulp stem cells, in clinical ocular surface reconstruction.

Keywords: Corneal epithelia; Limbus cornae; Stem cell; Dental pulp; Amniotic membrane; Ocular surface

Purpose: To evaluate the effects of ranibizumab and amfenac in human uveal melanoma cell lines and to explore the ability of these compounds to sensitize uveal melanoma cells to radiation therapy.
Methods: The 92.1 human uveal melanoma cell line was cultured and subjected to the proposed treatment (ranibizumab, amfenac, and a combination of both). Proliferation, migration, and invasion assays of the 92.1 uveal melanoma cell line were assessed after pretreatment with ranibizumab (125 µg/mLamfenac (150 nM), or a combination of both. In addition, proliferation rates were assessed after treatment with ranibizumab and amfenac, and the cells were subsequently exposed to various radiation doses (0, 4, and 8 Gy).
Results: Proliferation assay: cells treated with a combination of ranibizumab and amfenac had lower proliferation rates than controls (p=0.016) and than those treated with only ranibizumab (p=0.033). Migration assay: a significantly lower migration rate was observed in cells treated with amfenac than the control (p=0.014) and than those treated with ranibizumab (p=0.044). Invasion assay: there were no significant differences among the studied groups. Irradiation exposure: in the 4 Gy dose group, there were no significant differences among any groups. In the 8 Gy dose group, treatment with ranibizumab, amfenac, and their combination prior to application of the 8 Gy radiation led to a marked reduction in proliferation rates (p=0.009, p=0.01, and p=0.034, respectively) compared with controls.
Conclusion: Combination of ranibizumab and amfenac reduced the proliferation rate of uveal melanoma cells; however, only amfenac monotherapy significantly decreased cell migration. The radiosensitivity of the 92.1 uveal melanoma cell line increased following the administration of ranibizumab, amfenac, and their combination. Further investigation is warranted to determine if this is a viable pretreatment strategy to render large tumors amenable to radiotherapy.

Keywords: Uveal melanoma; Ranibizumab; Cyclooxygenase-2; Radiation; Cell line

Purpose: The aim of the present study was to compare the severity of ocular and systemic findings among patients with primary Sjögren syndrome.
Methods: The study followed a prospective controlled design and comprised two groups; the test group included 58 eyes of 58 patients newly diagnosed with primary Sjögren syndrome with poor dry eye test findings and the control group included 45 right eyes of 45 healthy age- and sex-matched individuals. The ocular surface disease index score, tear osmolarity, Schirmer I test without anesthesia, fluorescein tear breakup time, and cornea-conjunctiva staining with lissamine green (van Bijsterveld scoring) were used to examine tear function in the patients via a complete ophthalmological examination. The results were graded and classified on the basis of a Dry Eye WorkShop report and results of the corneal and conjunctival staining test, Schirmer’s test, and fluorescein tear breakup time test. Discomfort, severity and frequency of symptoms, visual symptoms, conjunctival injection, eyelid-meibomian gland findings, and corneal-tear signs were interpreted. Disease activity was scored per the EULAR Sjögren’s syndrome disease activity index (ESSDAI) via systemic examination and laboratory evaluations, and the EULAR Sjögren’s syndrome patient-reported index (ESSPRI) assessed via a survey of patient responses.
Results: Mean patient age was 48.15 ± 16.34 years in the primary Sjögren syndrome group and 44.06 ± 9.15 years in the control group. Mean fluorescein tear breakup time was 4.51 ± 2.89s in the primary Sjögren syndrome group and 10.20 ± 2.39 s in the control group. Mean Schirmer I test result was 3.51 ± 3.18 mm/5 min in the primary Sjögren syndrome group and 9.77±2.30 mm/5 min in the control group. Mean ocular surface disease index score was 18.56 ± 16.09 in the primary Sjögren syndrome group, and 19.92 ± 7.16 in the control group. Mean osmolarity was 306.48 ± 19.35 in the primary Sjögren syndrome group, and 292.54 ± 10.67 in the control group. Mean lissamine green staining score was 2.17 ± 2.76 in the primary Sjögren syndrome group, and 0.00 in the control group. Statistically significant differences were found berween the primary Sjögren syndrome group and control group in terms of fluorescein tear breakup time, Schirmer’s test, lissamine green staining, and osmolarity tests (p=0.036, p=0.041, p=0.001, and p=0.001 respectively). The Dry Eye WorkShop score was 2.15 ± 0.98, the EULAR Sjögren’s syndrome disease activity index score was 11.18 ± 4.05, and the EULAR Sjögren’s syndrome patient-reported index score was 5.20±2.63. When potential associations of the Dry Eye Workshop Study scores and osmolarity scores with the Eular Sjögren’s syndrome disease activity index scores were evaluated, the results were found to be statistically significant (p=0.001, p=0.001 respectively).
Conclusion: The results showed an association between dry eye severity and systemic activity index in primary Sjögren syndrome patients.

Keywords: Sjögren syndrome; Dry eye syndromes; Severity of illness index

Purpose: This study aimed to determine the variation in diameters of outer and inner apertures of eyedropper tips using a computer vision system. Standardizing the size of eye drop nozzles is crucial to reduce the treatment cost of chronic eye diseases and to ensure a continued use of medication. An eyedropper volume of >20 µL (maximum storage of the conjunctival sac) causes medication wastage and increases treatment costs.
Methods: We measured the diameters of the outer and inner apertures of eyedropper tips and evaluated variations in diameters using a computerized visual inspection system.
Results: The computer visual inspection system identified anomalies in the apertures of eyedropper tips that resulted in diameter variations.
Conclusions: The results of the present study show discrepancies in diameters of eyedropper tips, suggesting a variation in eyedropper size and medication wastage.

Keywords: Lubricant eye drops; Drug packaging; Eyedropp size; Diameter variation; Health care costs; Computer vision system

Purpose: The porcine eye is frequently used as a research model. This paper analyzes the effect of different storage methods on the transparency of pig crystalline lens.
Methods: A spectral transmission curve (from 220 to 780 nm) for the crystalline lens was determined experimentally after storage in different conditions: saline solution, formalin, castor oil, and freezing at -80°C. The total transmission in the visible spectrum, which was used as an index of transparency, was calculated from these curves. For comparative purposes, fresh lenses were evaluated and used as controls.
Results: Storing the porcine crystalline lens in saline solution or castor oil resulted in a transparency loss of approximately 10% after 24 h and storage in formalin resulted in a loss of nearly 30%. Storage by freezing at -80°C for 4 weeks maintained the transparency of the crystalline lens; the spectral transmission measured immediately after defrosting at room temperature coincided exactly with that of the freshly extracted lens.
Conclusions: The transparency of porcine crystalline lens is affected by the storage method. The visible spectrum is the most affected, evidenced by the effect on the transparency and consequently the amount of light transmitted. The results show that freezing at -80°C maintains the transparency of the crystalline lens for at least 4 weeks.

Keywords: Lens, crystalline; Organ preservation; Freezing; Animals; Swine

We report the case of a 4-year-old boy with Marfan syndrome whose parents reported he had had low visual acuity since birth. On examination, there was microspherophakia and a small subluxation of the lens. The objective refraction was -23.75 - 2.75 x 70 in the right eye and -25.50 -3.50 x 90 in the left eye. Since the microspherophakia and the high myopia severely affected the boy’s quality of life, clear lens extraction, anterior vitrectomy, posterior surgical capsulotomy via the pars plana, and intraocular lens implantation were performed. Two years postoperatively, the patient had centered intraocular lenses and a corrected visual acuity of 20/30 in both eyes. The child was satisfied with his vision and was able to study and perform daily activities without visual limitations.

Keywords: Marfan syndrome; Lens, intraocular; Lens implantation, intraocular; Lens, crystalline/surgery; Visual acuity; Humans; Child, preschool; Case reports

This report documents an unusual phenomenon. A 6-year-old girl with trochlear-oculomotor synkinesis presented with superior oblique and palpebral levator co-contraction. The literature was reviewed and the possibility of classifying this entity as a congenital cranial dysinnervation disorder was speculated.

Keywords: Synkinesis; Trochlear nerve; Cranial nerves/abnormalities; Oculomotor muscles; Ocular motility disorders/congenital; Case reports

The authors describe an unusual association between posterior keratoconus and iris atrophy, confirmed by a complete ocular evaluation, scheimpflug imaging and pachymetric curve. A hypothesis for concomitant findings is discussed.

Keywords: Keratoconus; Iris; Atrophy; Iridocorneal endothelial syndrome; Humans; Case reports

A 33-year-old male presented to our clinic with low vision in both eyes that started during the previous week. Visual acuity was 20/63 in the right eye and 20/50 in the left eye. Fundus examination revealed signs of hypertensive retinopathy; thus, a multidisciplinary approach was adopted for the diagnosis and treatment of this patient. We consulted the nephrology and cardiology departments on this case. Upon diagnosing malignant hypertension and renal failure, the patient was put on hemodialysis. His visual acuity was 20/20 at 6 months, whereas foveal assessment on optical coherence tomography angiography revealed neither marked superficial and deep capillary density loss and foveal avascular zone enlargement nor a decrease in disc flow and radial peripapillary capillary density. Early diagnosis and treatment of malignant hypertension are critical in preventing progression of end-organ damage including the eyes. Optical coherence tomography angiography may be useful in cases when fundus fluorescein angiography is relatively contraindicated (e.g., renal failure).

Keywords: Malignant hypertension; Tomography, optical coherence; Fluorescein angiography; Hypertensive retinopathy

The transparency and maintenance of corneal epithelial integrity are essential for its optical properties and, to preserve these characteristics, the epithelium undergoes continuous renewal. This renewal depends on the control of cell proliferation and differentiation mediated by mitogenic factors responsible for increasing mitoses and stimulating cellular migration. Cell-cell communication plays a pivotal role in epithelial healing process, and several cytokines and growth factors are involved in this process. Understanding the cross-talk and paracrine effects of these cytokines and growth factors released can help in the search for new therapeutic strategies to treat ocular surface diseases.

Keywords: Endothelium, corneal; Cytokines; Wound healing; Cell proliferation