VOLUME 80 - ISSUE 2

Purpose: We aimed to compare the retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, and the choroid thickness between patients with Behcet disease and healthy subjects by using spectral domain optical coherence tomography (SD-OCT). Methods: Ninety eyes of 45 healthy subjects and 104 eyes of 52 patients with Behcet disease were included in this study. Rheumatoid factor and C-reactive protein levels were measured by blood testing in the patients. Results: The mean thickness of the retinal nerve fiber layer, ganglion cells layer, and inner plexiform layer were significantly lower in patients with Behcet's disease than in the healthy subjects. The mean choroidal thickness was significantly higher in the patients than in the healthy subjects. Conclusions: SD-OCT was a useful and non-invasive tool for the detection of retinal nerve degeneration and choroidal changes in patients with Behcet disease even in the absence of ocular involvement.

Keywords: Retinal degeneration; tomography, optical coherence; Behcet disease/complications

Purpose: To investigate the effect of nicotinamide on the secretion of pro-an giogenic and pro-inflammatory cytokines in uveal melanoma cell lines. Methods: Two human uveal melanoma cell lines (92.1 and OCM-1) were treated with nicotinamide (10 mmol/L) or control media for 48 hours in culture. The su perna tant from each culture was used in sandwich enzyme-linked immuno sorbent assay-based angiogenesis and inflammation arrays to evaluate the effects of exogenously administered nicotinamide on the secretion of a total of 20 pro-an gio genic and pro-inflammatory proteins. Results: Seven pro-angiogenic cytokines were detected under control conditions for both uveal melanoma cell lines. Treatment with nicotinamide resulted in a significant decrease in secretion of the following pro-angiogenic cytokines: angiogenin, angiopoietin-2, epidermal growth factor, and vascular epithelial growth factor-A in the 92.1 cells; basic fibroblast growth factor in the OCM-1 cells; and placenta growth factor in both cell lines. Among the pro-inflammatory proteins, monocyte chemotactic protein-1 and interleukin-8 were expressed in both untreated cell lines and both were significantly reduced when treated with nicotinamide. Conclusions: Results from this in vitro model suggest that nicotinamide may have anti-inflammatory and anti-angiogenic properties, which may open the possibility of using it as a chemopreventive agent for uveal melanoma; however, further studies including animal models are warranted.

Keywords: Niacinamide; Cytokines; Uveal neoplasms; Melanoma; Vascular endothe lial growth factor A; Cell line

Purpose: To compare measurements of lesions clinically diagnosed as choroidal nevi using spectral domain optical coherence tomography (SD-OCT) and 10- and 20-MHz ultrasound (US). Methods: This prospective study, which was conducted between May 2011 and December 2011, evaluated eyes diagnosed with choroidal nevus via photographic documentation using 10- or 20-MHz A- and B-mode US (experienced examiner using both the transpalpebral technique and direct contact) or SD-OCT in the enhanced depth imaging mode (performed by a different examiner blinded to the US results). Anteroposterior (AP) and transverse (T) US sections corresponded to sections adjusted perpendicularly on SD-OCT. Results: We evaluated 14 eyes from 12 patients (six males, mean patient age= 64.5 years) diagnosed with choroidal nevus. The choroidal nevi of all samples had a melanocytic profile. Moreover, eight nevi were located at the equator, five nevi were located in the posterior pole (peripapillary in one sample), and one nevus shifted from the equator to the periphery. On SD-OCT, the maximum measurable dimension was 9 mm. The lesions in the posterior pole were easier to evaluate, and image acquisition of lesions located more peripherally was possible depending on patient cooperation. The accurate assessment of height was difficult. Baseline dimensions on 10- and 20-MHz US were larger than those determined via OCT. No significant differences in height were observed between US and SD-OCT. All parameters were statistically similar between 10- and 20-MHz US measurements. Conclusions: No significant difference in the AP and T diameters was observed between 10- and 20-MHz US measurements; however, these measurements (AP and T) were significantly higher than those obtained using OCT. No significant differences in height were observed among the techniques adopted.

Keywords: Choroidal neoplasms/ultrasonography; Nevus, pigmented/pathology; Tomography, optical coherence; Ultrasonography

Objective: Bacterial keratitis occurs worldwide, and despite recent developments, it remains a potentially blinding condition. This study assesses the presence of herpes simplex virus (HSV-1 and -2) and varicella zoster virus (VZV) by quantitative real-time polymerase chain reaction (qPCR) in corneal scrapings from patients with bacterial keratitis. Methods: A total of 65 patients with clinical diagnoses of infectious corneal ulcers prospectively underwent clinical eye examinations. Corneal scrapings were investigated by Gram staining, Giemsa staining, culture, and qPCR (the study group). Risk factors and epidemiological data were recorded. The control group comprising 25 eyes with typical herpes dendritic keratitis was also analyzed by qPCR. Results: From the study group (n=65), nine patients (13.8%) had negative smears, cultures, and qPCR findings. Fifty-six (86.2%) patients had positive cultures: 51 for bacteria, 4 for fungi, and 1 for amoebae. Of the patients who had positive bacterial cultures, qPCR identified 10 patients who were also positive for virus: one for VZV and nine for HSV-1. Of the 25 patients in the control group, 21 tested positive for HSV-1 by qPCR analysis. Conclusions: Herpes may be present in patients with bacterial corneal ulcers, and qPCR may be useful in its detection.

Keywords: Herpes simplex; herpesviridae; Keratitis, herpetic; Polymerase chain reaction

Purpose: To evaluate whether reducing eyelid muscular force through the administration of botulinum toxin type A (BTX-A) to the orbicularis oculi muscles of patients with keratoconus affected corneal parameters indicative of disease progression. Methods: In this prospective parallel randomized clinical trial, 40 eyes of 40 patients with keratoconus were randomized into equally sized control and BTX-A groups. Patients in the BTX-A group received subcutaneous BTX-A injections into the orbicularis muscle. The control group received no intervention. Palpebral fissure height, best spectacle-corrected visual acuity (BSCVA), and corneal topographic parameters were evaluated at baseline and at 3-, 6-, 12-, and 18-month follow-ups. Results: The mean ± standard deviation vertical palpebral fissure heights were 9.74 ± 1.87 mm and 9.45 ± 1.47 mm at baseline in the control and BTX-A groups, respectively, and 10.0 ± 1.49 mm and 9.62 ± 1.73 mm at 18 months, with no significant difference between the groups (p=0.337). BSCVA values were 0.63 ± 0.56 and 0.60 ± 0.27 at baseline in the control and BTX-A groups (p=0.643), and 0.52 ± 0.59 and 0.45 ± 0.26 at 18 months, again with no significant difference between the groups (p=0.452). In addition, there were no statistical differences between the groups at 18 months for the three keratometry topographic parameters: flattest (K1), steepest (K2), and mean (Km) keratometry (p=0.562). Conclusion: BTX-A inhibition of eyelid force generation did not result in detectable changes in corneal parameters in keratoconic patients during 18 months of follow-up.

Keywords: Corneal diseases; Keratoconus; eyelids; Botulinum toxins/therapeutic use

Purpose: We aimed to report and analyze topographic and refractive outcomes following corneal collagen crosslinking (CXL) in patients with progressive keratoconus (KC). Methods: We performed a retrospective, analytical, and observational study of 100 eyes from 74 progressive KC patients who underwent CXL at the Eye Hospital of Paraná. Keratometric values were analyzed preoperatively as well as 3 and 12 months postoperatively. Results: For a total of 100 eyes, 68 belonged to male patients. The mean age of our study population was 19.9 ± 5.61 years. The average visual acuity and topographic parameters overall were stable after 1 year (p<0.05). After 3 months, steepest keratometry reading (K2) and maximum keratometry (Kmax) were significantly decreased (p<0.05). Regarding topographic astigmatism (dK), there was no significant difference between the 3-month and 12-month follow-ups. When we made comparisons between genders following CXL, there were no significant differences related to the changes in Kmax, K2, and spectacle-corrected distance visual acuity (SCDVA). Conclusions: CXL promoted stabilization or improvement of keratometric values and visual acuity. We found that keratoconus apex stability may be achieved 3 months after the procedure. There was no significant difference in keratometric and refractive values measured between male and female patients.

Keywords: Corneal topography; Keratoconus/drug therapy; Riboflavin/therapeutic use; Collagen/radiation effects; Ultraviolet therapy

Purpose: To analyze the effects of injections of intravitreal triamcinolone acetonide (IVTA) and intravitreal bevacizumab (IVB) on the incidence rates of anterior segment neovascularization (ASN) and neovascular glaucoma (NVG) in patients with macular edema secondary to central retinal vein occlusion (CRVO). Methods: In this prospective, randomized, double-masked, sham-controlled study, 35 patients with macular edema following CRVO were randomized to intravitreal bevacizumab, intravitreal triamcinolone acetonide, or sham injections during the first 6 months of the study. The primary outcome was the incidence rate of ASN at month 6. The secondary outcomes were the mean changes from baseline in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) on optical coherence tomography over time to month 12. Results: ASN developed in 8 (22.86%) eyes, including 5 (62.50%) eyes in the sham group and 3 (37.50%) eyes in the IVTA group, during 12 months of fol low-up (p=0.009). BCVA differed significantly (p<0.05) among the groups only at month 1. CFT did not differ significantly (p<0.05) among the groups over 12 months. NVG required surgery and developed in one eye despite laser treatment. Conclusion: Early treatment with intravitreal antivascular endothelial growth factor therapy decreases the rates of ASN and NVG after CRVO.

Keywords: Neovascularization; Pathologic; Bevacizumab; Retinal vein occlusion; Macular edema; Glaucoma; Neovascular

Purpose: To evaluate the outcomes of phacoemulsification with intraocular lens (IOL) implantation in eyes with uveitis. Methods: Consecutive patients with uveitis and cataracts who had phacoemulsification and acrylic IOL implantation during 2007-2012 were evaluated for visual outcomes, etiology, and complications. Inflammation was controlled for at least 3 months before surgery, and oral prednisone (0.5 mg/kg/day) was administered to patients with non-infectious uveitis. Results: This study investigated 45 eyes in 38 patients with a mean age of 52 ± 12.5 years. The most common etiologies among non-infectious causes (n=32; 73.3%) were Vogt-Koyanagi-Harada disease (n=9), Fuchs heterochromic iridocyclitis (n=4), and sympathetic ophthalmia (n=3). Four cases were idiopathic. Among infectious cases (n=13; 28.9%), the most common causes were toxoplasmosis (n=6) and presumed ocular tuberculosis (n=4). An acrylic IOL was implanted in-the-bag in all cases. After 1-year follow-up, an improvement in visual acuity of two or more lines was observed in 38 eyes (84.4%), and 28 eyes (62.2%) achieved a postoperative visual acuity of ≥0.5. Posterior capsule opacification was observed in 10 eyes (22.2%). Persistent postoperative inflammation (of >6 months) was observed in seven eyes (15.5%) and recurrence occurred in four eyes (8.8%). IOL was explanted in one eye. Intraocular hypertension was observed in six eyes (13.3%). Conclusions: Phacoemulsification with IOL implantation improved vision in most patients with coexisting cataracts and uveitis. Good preoperative and postoperative control of inflammation plays an important role in achieving favorable visual outcomes. Furthermore, the final visual outcome depends on the posterior segment status.

Keywords: Uveitis; Cataract; Phacoemulsification; Visual acuity; Intraocular lens; Treatment outcome

Purpose: Avastin® (bevacizumab) is an anti-vascular endothelial growth factor (VEGF) monoclonal antibody given as an off-label drug by intravitreal administration for treatment of ocular diseases. The drug's clinical application and its cost-benefit profile has generated demand for its division into single-use vials to meet the low volume and low-cost doses necessary for intraocular administration. However, the safety of compounding the drug in single-use vials is still under discussion. In this study, the stability and efficacy of Avastin® repacked in individual single-use glass vials and glass ampoules by external compounding pharmacies were evaluated. Methods: Polyacrylamide gel electrophoresis (PAGE), size-exclusion chromatography (SEC), dynamic light scattering (DLS), and turbidimetry were selected to detect the formation of aggregates of various sizes. Changes in bevacizumab biological efficacy were investigated by using an enzyme-linked immunosorbent assay (ELISA). Results: Repacked and reference bevacizumab showed similar results when analyzed by PAGE. By SEC, a slight increase in high molecular weight aggregates and a reduction in bevacizumab monomers were observed in the products of the three compounding pharmacies relative to those in the reference bevacizumab. A comparison of repacked and reference SEC chromatograms showed that the mean monomer loss was ≤1% for all compounding pharmacies. Protein aggregates in the nanometer- and micrometer-size ranges were not detected by DLS and turbidimetry. In the efficacy assay, the biological function of repacked bevacizumab was preserved, with <3% loss of VEGF binding capacity relative to that of the reference. Conclusion: The results showed that bevacizumab remained stable after compounding in ampoules and single-use glass vials; no significant aggregation, fragmentation, or loss of biological activity was observed.

Keywords: Bevacizumab; Intravitreal injections; Macular edema/drug therapy; Drug stability

Purpose: Artisan iris-claw lens implantation (AICLI) is a surgical technique for treating ectopia lentis. We aimed to compare visual outcomes and possible long-term complications of AICLI surgery in pediatric patients with ectopia lentis with or without a diagnosable hereditary disease. Methods: Seventeen children with non-traumatic ectopia lentis were retros pectively classified into two groups: group 1 included children with a diagnosable hereditary disease (11 patients, 65%), and group 2 included children without any definable hereditary disease (six patients, 35%). Patients were evaluated for post-surgical refraction, best-corrected visual acuity, and clinical follow-up complications. Results: The average follow-up time was 38 months, and the average age of the patients was 103 ± 53 months (30-196 months). Best-corrected visual acuity values were significantly increased in both groups after surgery (p<0.05). Target refraction values were achieved at a rate of 47% in group 1 and 22% in group 2. Post-surgery complications, such as lens dislocation (36%, 11 eyes of 10 patients) and hypotonia (10%, three eyes of three patients) were observed in both groups, and retinal detachments (10%, three eyes of three patients) were observed in three patients from group 1. Conclusions: Compared with previous similar studies, this study utilized the largest pediatric patient group and had the longest post-surgery follow-up time. Moreover, it is advisable that pediatric patients with non-traumatic ectopia lentis be carefully screened for any underlying hereditary disease, especially diseases related to connective tissue metabolism.

Keywords: Lens implantation, intraocular/methods; Lenses, intraocular; Marfan syndrome/complications; Homocystinuria; Ectopia lentis/surgery

We report retinal functional and structural changes of a 40-year-old man diagnosed with occult macular dystrophy. Comprehensive ophthalmological evaluation was performed, followed by spectral-domain optical coherence tomography (SD-OC - Heidelberg) and image acquisition using an adaptive optics (AO) camera (RTX1, Imagine Eyes) for photoreceptor density analysis. Functional tests included full-field ERG (ERG) and multifocal electroretinography (mfERG) (Diagnosys, LLC) and microperimetry with scanning laser ophthalmoscope (SLO) fixation controlled (MAIA, CenterVUE). OCT revealed a line of discontinuity corresponding to cone outer-segment photoreceptors associated with a loss of cone density, highlighted by a dark blue spot on the AO co ne-density map on the fovea in both eyes. Loss of central sensitivity was revealed using microperimetry; ERG was within the normal range, although the mfERG showed a reduced central response amplitude.

Keywords: Macular degeneration/diagnosis; Photoreceptor cells; Visual field tests; Electroretinography; Tomography, optical coherence

Drusen are extracellular deposits between the basal lamina of the retinal pigment epithelium (RPE) and the inner collagenous layer of Bruch's membrane. Large colloid drusen (LCD) are located below the RPE and are characterized by multiple, large, dome-shaped RPE detachments, with marked attenuation of the ellipsoid zone overlaying the drusen. This report presents the structural en face optical coherence tomography (OCT) findings of LCD and relates them to findings from fluorescein and indocyanine green angiography. We describe the case of a 55-year-old woman who presented with the chief complaint of a 5-year history of progressively worsening vision. Her best-corrected visual acuities were 20/40 and 20/400 in the right eye and the left eye, respectively. Fundus examination showed large bilateral, symmetrical, sub-retinal, yellowish lesions compatible with LCD. We describe the structural en face OCT characteristics and angiographic findings from this patient.

Keywords: Retinal drusen; Tomography, optical coherence/methods; Fluorescein angiography; Indocyanine green

We report a case of ocular sarcoidosis with positive immunoglobulin (Ig) M and IgG serology for toxoplasmosis. The patient was a young female with red painful eyes, bilateral eyelid edema, and panuveitis with periphlebitis. In laboratory testing, she was IgM and IgG positive for toxoplasmosis and anergic in the tuberculin test. Topical treatment for anterior uveitis and oral antibiotics for toxoplasmosis were started, without improvement. Orbit tomography showed increased lacrimal glands bilaterally, and chest X-ray radiographic findings were consistent with pulmonary sarcoidosis, which supported the presumed ocular sarcoidosis diagnosis. The patient was treated with oral prednisone and methotrexate without antibiotics. She showed clinical and vision improvement without recurrences during the 1-year follow-up. Ocular sarcoidosis is an important differential diagnosis requiring careful anamnesis and ophthalmological examinations. Ancillary tests, such as X-ray radiography, tomography, and clinical and laboratory evaluations may help rule out other causes. Treatment mainly consists of corticosteroids and immunosuppression.

Keywords: Sarcoidosis; Toxoplasmosis, ocular; Uveitis, posterior; Eye diseases

Here we describe a rare case of a benign tumor in the lacrimal gland of a healthy 4-year-old girl. Mild proptosis was the only abnormality observed on clinical examination. Magnetic resonance imaging of the right orbit revealed an oval, solid, well-circumscribed, homogeneous mass extending from the lacrimal gland and measuring 2.5 × 2.3 × 1.7 cm without any evidence of invasion into adjacent bones. The lesion was surgically excised and histological analyses defined the diagnosis of oncocytoma of the lacrimal gland. Although rare, oncocytoma should be included in the differential diagnosis of lacrimal gland tumors.

Keywords: Adenoma, oxyphilic; Lacrimal gland; Exophthalmos; Orbital neoplasms; Magnetic resonance imaging; Child, preschool; Case reports

In this systematic review, we evaluated studies involving adjuvant and primary topical treatment for ocular surface squamous neoplasia (OSSN). The findings were: (i) adjuvant 5-fluorouracil (5-FU) reduces the risk of relapse after surgical excision with mild side effects [level Ib, grade of recommendation (GR) A]. (ii) Primary topical mitomycin (MMC) produces a high rate of complete response, low recurrence rate, and mild side effects (level Ib, GR A). (iii) Primary chemotherapy versus adjuvant chemotherapy produce similar rates of recurrence, with no significant difference (level IIb, GR B). (iv) Adjuvant 5-FU versus MMC showed no significant differences, with mild side effects in both groups and a better toxicity profile for MMC (level III, GR C). (v) Primary topical 5-FU versus MMC versus interferon (IFN) showed similar rates of tumor recurrence, mild side effects for all drugs, and more severe side effects in the 5-FU arm, followed successively by MMC and IFN (level III, GR C).

Keywords: Carcinoma, squamous cell; Eye neoplasms; Fluorouracil; Interferons; Mitomycin; Review