VOLUME 79 - ISSUE 6

Purpose: We evaluated the efficacy of lycopene, a dietary carotenoid and potent antioxidant, against ocular inflammation and oxidative stress in an experimental uveitis model. Methods: Endotoxin-induced uveitis (EIU) was induced in Sprague-Dawley rats by a single subcutaneous injection of 200 μg lipopolysaccharide (LPS). Induction of EIU was preceded by daily intraperitoneal injection of 10 mg/kg lycopene for three consecutive days (Lycopene + LPS group) or equivolume vehicle (Vehicle + LPS group). A positive control group received 1 mg/kg dexamethasone pretreatment (DEX + LPS), and a negative control group received daily vehicle injection but no LPS (Vehicle Control). Twenty-four hours after LPS or final vehicle administration, eyes were enucleated, and aqueous humor was collected for measurement of the number of infiltrating cells, total protein concentration, and levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and oxidative stress markers. Inflammatory response severity was compared among groups clinically and histopathologically. Results: Infiltrating cell number, total protein concentration, and NO, TNF-α, and IL-6 levels were significantly elevated in the aqueous humor of Vehicle + LPS group rats compared to Vehicle Controls. Compared to the Vehicle + LPS group, lycopene pretreatment significantly reduced aqueous humor concentrations of oxidative stress markers, NO (0.29 ± 0.1 μM vs. 0.19 ± 0.1 μM, p=0.003), TNF-α (71.0 ± 22.3 ng/ml vs. 50.1 ± 2.1 ng/ml, p=0.043), and IL-6 (121.6 ± 3.0 pg/ml vs. 111.1 ± 5.6 pg/ml, p=0.008). Inflammatory score was also reduced (2.0 ± 0.0 vs. 0.4 ± 0.5, p=0.001). Lycopene reduced the infiltrating cell count and protein concentration, but differences did not reach significance. Most lycopene effects were equivalent to dexamethasone. Conclusions: Lycopene may aid in the clinical management of uveitis by suppressing inflammation and oxidative stress.

Keywords: Uveitis/chemically induced; Endotoxins; Oxidative stress; Antioxidants; Inflammation; Cytokines; Animals; Disease models, animal; Rats

Purpose: This study aimed to explore the effects of the Valsalva maneuver (VM) on ectatic corneas during anterior segment tomography scans using a Scheimpflug camera. Methods: This prospective observational study included 100 eyes of 50 patients with bilateral keratoconus (KC). Anterior segment tomography was first performed when the patients were in a resting position and immediately repeated as the participant performed VM. Scheimpflug images were taken using a Pentacam®. Results: The mean age of the participants was 24.14 ± 6.59 years. Of the 100 eyes included in the study, 7% had stage 1 KC, 47% had stage 2 KC, 32% had stage 3 KC, and 14% had stage 4 KC. The indices of KC were not significantly affected by VM. Similarly, no statistically significant differences were found between the stages of KC, or with the mean pachymetric progression index during VM. Pupil diameter showed a statistically significant increase during VM (p=0.017). There was a statistically significant decrease in the anterior chamber angle measurement during VM (p=0.001). Maximum curvature power in the front of the cornea decreased more during VM in stage 4 KC than for the other stages (p=0.014). Conclusions: No changes associated with VM were found in the KC indices or the stage of the disease. However, an increase in pupil diameter and a decrease in anterior chamber angle value were found. These changes were comparable to values obtained from previous studies performed on normal corneas.

Keywords: Anterior chamber/physiology; Keratoconus; Valsalva maneuver/physiology; Corneal topography

Purpose: The optical quality of the interface after deep anterior lamellar keratoplasty (DALK) using the big-bubble technique has been shown to be excellent, leading to results comparable to penetrating keratoplasty. However, there is little in the literature with respect to the controversy surrounding the preparation of the donor cornea. The purpose of this study was to evaluate visual acuity (VA) in patients with keratoconus who underwent DALK without removal of the donor graft endothelium. Methods: The records of 90 patients who underwent DALK without the removal of the Descemet membrane (DM) and endothelium were retrospectively reviewed. Data collected included uncorrected VA (UCVA) and spectacle-corrected VA (SCVA) at 7, 30, 180 days, and 1 year postoperatively. Contact lens-corrected visual acuity (CLVA) was evaluated after 1 year of the procedure. Results: UCVA was significantly better than preoperative values at 7 days (p<0.001), 30 days (p<0.001), 180 days (p<0.001), and 1 year (p<0.001) after surgery. The 1-year postoperative mean SCVA and CLVA also improved when compared with preoperative SCVA (p<0.001 for both). Conclusions: DALK utilizing donor corneas with attached Descemet membrane and endothelium results in satisfactory VA in patients with keratoconus.

Keywords: Corneal diseases/surgery; Descemet membrane/surgery; Corneal transplantation/methods; Endothelium, corneal; Keratoplasty, penetrating; Keratonoconus/surgery; Visual acuity

Purpose: To evaluate the efficacy and tolerance of mycophenolate mofetil (MMF) for the treatment of noninfectious uveitis using the methods advocated by the Standardization of Uveitis Nomenclature (SUN) Working Group and to compare this with other studies of immunosuppression in ocular inflammation. Methods: Retrospective case series. Patients with noninfectious uveitis, followed at a tertiary Uveitis Service in São Paulo, Brazil, from 2007 to 2014 and receiving oral MMF for a minimum of 6 months, were retrospectively reviewed. After reaching an optimal dose of MMF, patients were evaluated after 6 (T6), 12 (T12), and 24 months (T24). The optimal dose varied for each patient (medium 2.2 g/day, range 1.0-3.0 g/day). The main outcome measures were: 1) success on achieving complete control of inflammation in both eyes and/or oral prednisone dosage reduction to ≤10 mg per day, and 2) the length of time required to reduce oral prednisone to ≤10 mg/day, partial control of ocular inflammation, and side effects. Results: In a cohort of 16 patients with refractory noninfectious uveitis, 67% reached the ideal prednisone dose after 1 year of MMF treatment and 83% after 2 years of MMF treatment. Complete or partial inflammation control was achieved in 43.7% at T12. Two patients (14%) had disease remission after 4.7 years of MMF treatment. Adverse effects were gastrointestinal disturbances, infection, insomnia, and liver function abnormalities at a rate of 0.03 patient-year each. Conclusions: This small retrospective case series is consistent with the literature concerning the high efficacy and moderate tolerability of MMF in noninfectious uveitis. Observation of patients should be continued for at least 1 year to clearly determine MMF efficacy.

Keywords: Uveitis, chronic; Immunosuppressive agents; Mycophenolate mofetil

Purpose: To investigate the influence of the epiretinal membrane (ERM) on intravitreal ranibizumab (IVR) therapy for diabetic macular edema (DME). Methods: This retrospective study included 56 eyes of 48 patients with DME divided into two groups: the DME with ERM (study) and only DME (control) groups. Changes in the central macular thickness (CMT) and best-corrected visual acuity (BCVA) were evaluated. Results: In the study group, although the CMT was significantly reduced following the first injection (p<0.001), BCVA did not improve significantly (p=0.296). However, after the first injection, the control group exhibited both a significant decrease in CMT (p<0.001) and improvement in BCVA (p<0.001). However, the improvement in BCVA in the control group was not significantly different from the outcome of the study group. Conclusions: We observed a negative short-term influence of the ERM on IVR treatment for DME.

Keywords: Epiretinal membrane; Macular edema; drug therapy; Retinopathy; diabetic complications; Ranibizumab/therapeutic use

Purpose: To evaluate the long-term outcomes of medically or surgically treated patients with atopic keratoconjunctivitis (AKC). Methods: Charts of 16 patients with AKC (32 eyes) observed between 1996 and 2013 were reviewed retrospectively. Outcome measures included demographic features, follow-up duration, and biomicroscopic findings at the first and most recent visits. The corrected distance visual acuity (CDVA; in decimal units) was evaluated at the initial visit and the 1-, 6-, and 12-month follow-up visits. Results: In the medically treated group (25 eyes of 15 patients), the median follow-up duration was 3 (range, 1-9) years, and the median CDVA values were 0.01 (0.001-1.0) at the first visit and 0.01 (0.001-0.8) at the most recent visit (p=0.916). In the penetrating keratoplasty (PK) group (7 eyes of 6 patients), the median follow-up duration was 7 years (range, 1-11), and the median CDVA increased from 0.01 (0.001-0.01) to 0.2 (0.001-0.7) postoperatively (p=0.043). Conclusion: Whereas most AKC patients maintained a useful CDVA with medical treatment, PK may be required in some cases. Despite the frequent occurrence of complications, PK can significantly improve the CDVA.

Keywords: Conjunctivitis, allergic/therapy; Conjunctivitis, allergic/surgery; Keratoplasty, penetrating; Treatment outcome

Purpose: To investigate the relationship between biomechanical properties of the cornea and postoperative refractive changes in patients with low-level astigmatism after cataract surgery. Methods: This prospective study recruited patients undergoing cataract surgery involving 2.8-mm superior incisions. Biomechanical properties of the cornea were evaluated preoperatively using the Ocular Response Analyzer, and corneal profiles were evaluated using a Scheimpflug system (Pentacam HR). Topographic astigmatism, total corneal aberrations (TCA) and higher-order corneal aberrations (HOCA) analyses were performed preoperatively and during 1- and 3-month postoperative exams. The incidences of surgically-induced astigmatism (SIA) and HOCAs were calculated using vector analyses. Associations of the preoperative biomechanical properties of the cornea with SIA and HOCAs were evaluated. Results: This study included 28 eyes of 28 patients. The preoperative corneal hysteresis (CH) was 8.68 ± 1.86 mmHg, and the corneal resistance factor (CRF) was 8.66 ± 1.61 mmHg. At the 1-month postoperative evaluation, significant changes were observed in HOCAs (p=0.023), TCAs (p=0.05), astigmatism (p=0.02), and trefoil (p=0.033); in contrast, differences in coma (p=0.386) and spherical aberration (SA) were not significant (p=0.947). At the 3-month visit, significant changes were only observed in TCAs (p=0.02) and HOCAs (p=0.012). No relationships between the preoperative corneal hysteresis and corneal resistance factor and postoperative SIA and HOCA were identified, other than a positive correlation between the 3-month postoperative incidence of corneal hysteresis and spherical aberration. Conclusions: Despite the observed lack of relationships of preoperative biomechanical properties of the cornea with SIA and postoperative aberrations (except for SA), further studies involving larger patient groups are needed to explore the unexpected refractive deviations after cataract surgery.

Keywords: Cornea/surgery; Cornea/physiopathology; Cataract extraction; Lens implantation, intraocular; Biomechanical phenomena/physiology; Corneal wavefront aberration/physiopathology; Astigmatism/etiology

Purpose: The present study compared the efficacy of aflibercept for neovascular age-related macular degeneration (NV-AMD) in patients with complete ranibizumab resistance and tachyphylaxis. Methods: Forty-four eyes of 38 neovascular age-related macular degeneration patients were evaluated. Eyes were divided into a complete resistance group (n=23 eyes) and tachyphylaxis group (n=21 eyes). Results: After three injections, eight (38.1%) patients in the tachyphylaxis group and nine (39.1%) in the complete resistance group presented with macular dryness. After the first injection of aflibercept, the mean visual acuity improved significantly in the tachyphylaxis group (p=0.018) but remained unchanged in the complete resistance group (p=0.37). There was a non-significant trend towards improved mean visual acuity in both groups after the second and third injections relative to the acuity at the final visit for ranibizumab treatment. In the tachyphylaxis group, the presence of subfoveal pigmented epithelium detachment (PED) decreased significantly after intravitreal aflibercept treatment. Conclusions: Although treatment with aflibercept yielded generally positive anatomical results in both groups, no significant increase in visual acuity was achieved.

Keywords: Angiogenesis inhibitors; Macular degeneration; Ranibizumab; Tachyphylaxis; Vascular endothelial growth factor A

Purpose: Alternative recording methods have been tested to allow the electroretinogram (ERG) recording in uncooperative patients and/or patients with palpebral alterations, including recordings with skin electrodes. The purpose of this study was to compare ERG recorded with skin electrodes and well-established microfiber electrodes and to determine normative values of ERG parameters for recording with skin electrodes. Methods: Fifty healthy volunteers (17-26 years; mean 20.63 ± 2.01 years) participated in the study. A gold disk skin electrode was placed on the lower orbital rim of a randomly chosen eye. On the contralateral eye, a microfiber electrode was positioned in the lower conjunctival sac. Gold disc electrodes were positioned at the ipsilateral outer canthus of both eyes acting as reference electrodes for the creation of a potential difference. Two ground electrodes were placed on the lobe of each ear. ERGs were recorded according to the International Society of Clinical Electrophysiology Visual (ISCEV) protocol using the VERIS 5.1.9 system for data acquisition and analysis. Results: Both types of electrodes showed similar wave response morphologies. The implicit time of responses between the two electrodes was comparable. On peak-to-peak amplitude, skin electrode recordings showed an amplitude reduction of 61.4% for rod responses, 61.5% for maximal responses, 46.2% for oscillatory potentials, 57.4% for cone responses, and 54.4% for 30Hz-flicker responses, when compared with microfiber electrode recordings. Based on these findings, normative values for peak-to-peak amplitude and implicit time to be used as a reference for ERGs recorded with skin electrodes were determined. Conclusions: ERGs recorded with skin electrodes presented lower peak-to-peak amplitude compared with microfiber electrodes. However, using appropriate normative values, skin electrodes may be useful for specific target populations such as uncooperative infants and/or patients with ocular surface alterations.

Keywords: Electroretinography; Electrodes; Skin; Eyelids; Comparative study

Purpose: The cellular origin of retinoblastoma is uncertain as constituent tumor cells heterogeneously express markers of both immature and mature retinal cells. An immunohistochemical analysis of cellular origin may yield valuable insights into disease progression and treatment options. This study aimed to determine the cellular origin of retinoblastoma in a large case series and correlate these findings with histopathological prognostic factors. Methods: Thirty-nine retinoblastoma cases were histopathologically diagnosed and analyzed by immunohistochemistry using monoclonal antibodies against the immature neural cell marker SRY-box containing gene 2 (SOX-2), the mature neuronal cell marker microtubule-associated protein 2 (MAP2), and the mature glial cell marker glial fibrillary acidic protein (GFAP). Histopathological features were also evaluated, including patterns of growth, differentiation, vitreous seeding, and choroidal/scleral, optic nerve, and anterior chamber invasion. Two retinoblastoma cell lines, WERI-1 and Y79, were studied by immunocytochemistry using the same antibodies. Results: Expression of SOX-2 was strong in 97.4% of retinoblastoma cases, while MAP-2 was expressed in 59% of cases. Immunostaining for GFAP was positive only in reactive stromal astrocytes interspersed amongst tumor cells and in peritumoral tissue. There was no correlation between histopathological prognostic factors and immunohistochemical markers. Retinoblastoma cell lines showed strong positivity for SOX2 (90% of WERI-1 cells and 70% of Y79 cells) and MAP2 (90% of cells in both lines). GFAP was completely negative in both cell lines. Conclusion: The majority of retinoblastomas and both RB cell lines expressed an immature neural and/or a mature neuronal cell marker, but not a glial marker. These results indicate a typical neuroblast or neuronal origin and eliminate astrocyte differentiation from neural stem cells as the source of retinoblastoma.

Keywords: Retinoblastoma/etiology; Retinoblastoma/pathology; Phenotype; Prognosis; Immunohistochemistry; Antibodies, monoclonal

This case report describes the retinal optical coherence tomography (OCT) findings in a microcephalic infant with macular atrophy presumably caused by intrauterine Zika virus infection. OCT demonstrated atrophy of the outer retinal layers and choriocapillaris, including the outer nuclear layer and ellipsoid zone, associated with retinal pigment epithelium hyper-reflectivity and increased OCT penetration into deeper layers of the choroid and sclera. A major concern associated with this infection is the apparent increased incidence of microcephaly in fetuses born to mothers infected with the Zika virus. It is becoming increasingly difficult to ignore the upsurge in congenital microcephaly observed in Brazil. Recently, ocular findings in infants with microcephaly associated with intrauterine Zika virus infection have been described. This is the first report of OCT imaging of macular atrophy in a child with presumed Zika virus infection-associated microcephaly.

Keywords: Retina; Microcephaly; Zika virus; Tomography, optical coherence; Eye manifestations

Lichen planus (LP) is an autoimmune, inflammatory disease of unknown etiology that commonly affects the skin and mucous membranes. Retinal vasculitis is a group of vision-threatening disorders, in which autoimmunity is thought to play a role in pathogenesis. We present the case of a patient who was diagnosed with retinal vasculitis and who was followed up for mucosal LP. LP has not been reported as a cause of retinal vasculitis in the literature. We believe that the retinal vasculitis in this case was related to LP because cellular immunity plays a role in the pathogenesis of both entities.

Keywords: Retina; Retinal vasculitis; Lichen planus; Fluorescein angiography

Here we report a case of surgical pupilloplasty in an adult with true polycoria. A 44-year old man was referred to our clinic with a best-corrected visual acuity (BCVA) of 0.5 diopters (D) in his left eye. Biomicroscopy revealed two pupils within a 2.5-mm central zone, with diameters of 1.2 and 1.1 mm. Both pupils had real iris sphincters and responded to light and chemical stimulation. Therefore, we surgically cut the bridge between the two pupils without any intraoperative or postoperative complications. One month after the surgery, BCVA had improved to 0.9 D, and the final pupil was almost round, measuring 2.7 mm in diameter.

Keywords: Iris/abnormalities; Pupil/abnormalities; Pupil/surgery

Ocular metastasis is relatively uncommon, with a reported incidence of approximately 8%, according to the results of autopsy evaluation. The majority of ocular metastases are located within the choroid, while metastatic tumors affecting the iris are rare. Metastatic tumors may manifest as stromal nodules or ill-defined iris thickening, or they may present with nonspecific features such as pain, iridocyclitis, and hyphema. Here, we describe three patients with iris metastasis and discuss the diagnostic challenges and unusual findings associated with these cases.

Keywords: Iris neoplasms; Iris metastasis; Case reports

We present two patients with dacryoliths and patent lacrimal drainage with intermittent tearing and without infection. Dacryoliths can be present in the lacrimal sac or lacrimal duct without acute or chronic inflammation. In these cases, we believe dacryolith formation was a causative factor of intermittent epiphora even with a patent drainage system, and we propose that dacryoliths and even fungal colonization formation may be the first event before dacryocystitis and should be considered as a cause of epiphora.

Keywords: Lacrimal apparatus diseases; Dacryocystitis

A 21-year-old female presented with a 4-day history of decreased vision in her only functional eye (right eye, OD). She had a history of multiple ocular surgeries in both eyes because of congenital glaucoma and had lost light perception in her left eye several years prior. Ophthalmological examination revealed 0.15 Snellen visual acuity, and fundoscopy revealed nearly total cupping and pallor of the optic disc and multiple retinal hemorrhagic foci in the macula in OD. Lesions spontaneously resolved over a few months. Gravitational forces during a roller coaster ride may have caused this macular hemorrhage.

Keywords: Eye hemorrhage; Tomography, optical coherence; Glaucoma/congenital

Although eye drops are frequently used as an initial treatment option for open angle glaucoma (OAG), side effects, and poor adherence, among others, may compromise treatment efficacy. In this scenario, laser trabeculoplasty is an interesting therapeutic option for open angle glaucoma cases. Commonly used for many years as a last alternative prior to glaucoma incisional surgery, laser trabeculoplasty has been changing its indication after the advent of selective laser trabeculoplasty (SLT). In the current review, we critically evaluated the published data regarding the use of laser trabeculoplasty as a first treatment option for open angle glaucoma patients. Studies using SLT as a first-line treatment have encouraging findings. One-year efficacy results are comparable to those obtained with prostaglandin analogues, with a good safety profile. Although the laser´s effect is known to be transitory, recent data suggest it can be successfully repeated in cases with good response to the first SLT treatment.

Keywords: Glaucoma, open-angle/surgery; Trabeculectomy/methods; Lasers; Intraocular pressure