Influence of the eye-tracking-based follow-up function in retinal nerve fiber layer thickness using fourier-domain optical coherence tomography.

PURPOSE: To evaluate the eye-tracking-based follow-up (EBF) function in the reproducibility of the peripapillary retinal nerve fiber layer (RNFL) thickness measurements obtained with Fourier-domain optical coherence tomography (Fd-OCT). METHODS: Thirty healthy subjects were imaged on an Fd-OCT device at the same visit by two examiners. Peripapillary circular scans in "high-speed" (HS) mode with the "automatic real time" (ART) set at 16 and in "high-resolution" (HR) mode with the ART off were obtained without and with the EBF function activated. RESULTS: Mean (± SD) global RNFL thickness was 105.1 (± 9.5) µm on HS mode and 105.4 (± 9.6) µm on HR mode. Interobserver analysis for global RNFL thickness revealed an intraclass correlation coefficient (ICC) greater than or equal to 0.96 for all but the HR mode without the use of EBF function (ICC = 0.73). Intraobserver analysis for global RNFL thickness revealed an ICC greater than 0.98 for all but the HR mode without the use of EBF function (ICC = 0.86). The interobserver and intraobserver analyses revealed the lowest ICC values for the temporal region on both HS and HR modes. Higher ICC values were obtained with the HS mode and when the EBF function was activated, particularly when using the HR mode. CONCLUSIONS: The EBF function had no influence in the reproducibility of the global peripapillary RNFL thickness measurements in healthy subjects on HS mode with ART on. However, reproducibility of the global RNFL thickness measurements on HR mode as well as of the temporal and temporal superior regions in both HS and HR modes was greater with the EBF function.

Randomized clinical trial evaluating mETDRS versus normal or high-density micropulse photocoagulation for diabetic macular edema.

PURPOSE: To compare modified Early Treatment Diabetic Retinopathy Study (mETDRS) focal/grid laser photocoagulation with normal-density (ND-SDM) or high-density (HD-SDM) subthreshold diode-laser micropulse photocoagulation for the treatment diabetic macular edema (DME). METHODS: A prospective, randomized, controlled, double-masked clinical trial with patients with previously untreated DME and best corrected visual acuity (BCVA) worse than 20/40 and better than 20/400. Patients were randomized to receive either mETDRS focal/grid photocoagulation (42 patients), ND-SDM (39 patients), or HD-SDM (42 patients). Before treatment and 1, 3, 6, and 12 months after treatment, all patients underwent ophthalmic examinations, BCVA, color fundus photography, fluorescein angiography, and optical coherence tomography (OCT). RESULTS: At 12 months, the HD-SDM group had the best improvement in BCVA (0.25 logMAR), followed by the mETDRS group (0.08 logMAR), whereas no improvements were seen in the ND-SDM group (0.03 logMAR). All groups showed statistically significant progressive reduction of central macular thickness (CMT) throughout the study (P < 0.001). The HD-SDM group exhibited the greatest CMT reduction (154 µm), which was not significantly different from that of the mETDRS group (126 µm; P = 0.75). CONCLUSIONS: At 1 year, the clinical performance of HD-SDM was superior to that of the mETDRS photocoagulation technique, according to the anatomic and functional measures of improvement used in this investigation. A rationale for this treatment modality as a preferable approach is suggested, and the precise role of subthreshold micropulse laser treatment may become more defined as experience grows, guided by optimized treatment guidelines and more comprehensive trials. (Clinicaltrials.gov number, NCT00552435.).

Controlled transscleral drug delivery formulations to the eye: establishing new concepts and paradigms in ocular anti-inflammatory therapeutics and antibacterial prophylaxis.

IMPORTANCE OF THE FIELD: The use of topical agents poses unique and challenging hurdles for drug delivery. Topical steroids effectively control ocular inflammation, but are associated with the well-recognized dilemma of patient compliance. Although administration of topical antimicrobials as prophylaxis is acceptable among ophthalmologists, this common practice has no sound evidence base. Developing a new antimicrobial agent or delivery strategy with enhanced penetration by considering the anatomical and physiological constraints exerted by the barriers of the eye is not a commonly perceived strategy. Exploiting the permeability of the sclera, subconjunctival routes may offer a promising alternative for enhanced drug delivery and tissue targeting. AREA COVERED IN THIS REVIEW: Ocular drug delivery strategies were reviewed for ocular inflammation and infections clinically adopted for newer class of antimicrobials, which use a multipronged approach to limit risks of endophthalmitis. WHAT THE READER WILL GAIN: The analysis substantiates a new transscleral drug delivery therapeutic approach for cataract surgery. TAKE HOME MESSAGE: A new anti-inflammatory and anti-infective paradigm that frees the patient from the nuisance of topical therapeutics is introduced, opening a large investigative avenue for future improved therapies.

Subconjunctival delivery of antibiotics in a controlled-release system: a novel anti-infective prophylaxis approach for cataract surgery.

OBJECTIVE: To compare the efficacy of subconjunctival injection of a combination of triamcinolone and ciprofloxacin hydrochloride, 2 mg/0.1 mL, in a controlled-release system (DuoCat) with that of ciprofloxacin hydrochloride, 0.3%, eyedrops for infection prophylaxis. METHODS: Rabbit eyes were injected subconjunctivally with a combination of triamcinolone and ciprofloxacin hydrochloride, 2 mg/0.1 mL, or ciprofloxacin hydrochloride, 2 mg/0.1 mL, alone. The aqueous and vitreous humor pharmacokinetic profiles were compared with those of a single drop of ciprofloxacin hydrochloride, 0.3%, 6 times daily. In 45 rabbits, Staphylococcus aureus was injected into the anterior chamber: 15 randomly received 1 drop of ciprofloxacin hydrochloride, 0.3%, every 4 hours during 24 hours; 15 received drops of balanced salt solution; and 15 received a combination of triamcinolone and ciprofloxacin hydrochloride, 2 mg/0.1 mL. After 24 hours, endophthalmitis scores were recorded, aqueous and vitreous humors underwent culture, and histologic analysis was performed. RESULTS: The combined triamcinolone and ciprofloxacin treatment allowed higher intraocular levels of ciprofloxacin. The median endophthalmitis clinical scores for the combination of triamcinolone and ciprofloxacin and ciprofloxacin-only eyedrop groups were equivalent (P = .42) and were significantly lower than those of the balanced salt solution group (P < .001). The culture was negative for S aureus in the combined triamcinolone and ciprofloxacin and ciprofloxacin eyedrop regimens. No adverse effects were observed with either route. CONCLUSIONS: Ciprofloxacin eyedrops and combined triamcinolone and ciprofloxacin were equally tolerated and efficacious. The combined triamcinolone and ciprofloxacin treatment may eliminate noncompliance issues and may prove to be a valuable clinical tool for surgical prophylaxis. CLINICAL RELEVANCE: The combined triamcinolone and ciprofloxacin treatment may be a new useful strategy for surgical prophylaxis.

Effect of diabetic retinopathy and panretinal photocoagulation on retinal nerve fiber layer and optic nerve appearance.

OBJECTIVE: To determine if panretinal photocoagulation (PRP) alters retinal nerve fiber layer (RNFL) thickness and optic nerve appearance. METHODS: Patients with diabetes who did and did not undergo PRP and nondiabetic control subjects were enrolled in a prospective study. Participants underwent optical coherence tomography of the peripapillary retina and optic nerve. Stereoscopic optic nerve photographs were graded in a masked fashion. RESULTS: Ninety-four eyes of 48 healthy individuals, 89 eyes of 55 diabetic patients who did not undergo PRP, and 37 eyes of 24 subjects with diabetes who underwent PRP were included in this study. Eyes that had been treated with PRP had thinner peripapillary RNFL compared with the other groups; this was statistically significantly different in the inferior (P = .004) and nasal (P = .003) regions. Optic nerve cupping did not increase with severity of disease classification, but the proportion of optic nerves graded as suspicious for glaucoma or as having nonglaucomatous optic neuropathy did (P = .008). These grading categories were associated with thinner RNFL measurements. CONCLUSIONS: Diabetic eyes that have been treated with PRP have thinner RNFL than nondiabetic eyes. Optic nerves in eyes treated with PRP are more likely to be graded as abnormal, but their appearance is not necessarily glaucomatous and may be related to thinning of the RNFL.

Intravitreal bevacizumab for diabetic macular edema associated with severe capillary loss: one-year results of a pilot study.

PURPOSE: To evaluate the effects of intravitreal bevacizumab in patients with diabetic macular edema (DME) associated with severe capillary loss. DESIGN: Multicenter, open-label, nonrandomized study. SETTING: Two tertiary ophthalmic referral centers in Brazil. STUDY POPULATION: Ten consecutive patients with DME and "severe" capillary loss. OBSERVATION PROCEDURES: Intravitreal injection(s) of bevacizumab (1.5 mg). Standardized ophthalmic evaluation was performed at baseline and at weeks 8, 16, 24, and 54. MAIN OUTCOME MEASURES: Changes in best-corrected visual acuity (BCVA) and in optical coherence tomography variables (central macular thickness [CMT] and total macular volume [TMV]). RESULTS: Significant changes in BCVA and in CMT/TMV were noted throughout the study (P < .001, P = .009, and P < .001, respectively). The mean logarithm of the minimal angle of resolution Early Treatment Diabetic Retinopathy Study BCVA was 0.786 ( approximately 20/125(+1)) at baseline, 0.646 ( approximately 20/80(-2)) at week 8, 0.580 (20/80(+1)) at week 16, 0.574 ( approximately 20/80(+1)) at week 24, and 0.558 ( approximately 20/80(+2)) at week 54. Compared with baseline, a significant change in BCVA was noted at all follow-up visits (P

A single intraoperative sub-tenon's capsule injection of triamcinolone and ciprofloxacin in a controlled-release system for cataract surgery.

PURPOSE: To compare intraoperative injection of triamcinolone and ciprofloxacin in a controlled-release system (DuoCat) with prednisolone and ciprofloxacin eye drops after cataract surgery. METHODS: In this randomized, double-masked, controlled trial, a total of 135 patients undergoing cataract surgery were randomly allocated to two groups: 67 patients treated after surgery with prednisolone 1% and ciprofloxacin 3% eye drops four times daily (week 1), three times daily (week 2), twice daily (week 3), and once daily (week 4) and 0.3% ciprofloxacin drops four times daily (weeks 1 and 2), and 68 patients treated at the end of surgery with a sub-Tenon's injection of 25 mg triamcinolone and 2 mg ciprofloxacin in biodegradable microspheres. The patients were examined on postoperative days 1, 3, 7, 14, and 28. The main outcome measures were postoperative anterior chamber cell and flare, intraocular pressure (IOP), lack of anti-inflammatory response, and presence of infection. RESULTS: No significant differences were observed between the groups in anterior chamber cell (P > 0.14) and flare (P > 0.02) at any postoperative visits. The mean (99% confidence interval) differences in IOP between the prednisolone and triamcinolone groups on days 1, 3, 7, 14, and 28 were -0.4 mm Hg (-2.1 to 1.3), 0.0 mm Hg (-1.4 to 1.3), 0.0 mm Hg (-1.1 to 1.1), -0.2 mm Hg (-1.1 to 0.8), and -0.1 mm Hg (-1.1 to 0.9), respectively. No patient had a postoperative infection. CONCLUSIONS: One injection of DuoCat had a therapeutic response and ocular tolerance that were equivalent to conventional eye drops in controlling inflammation after cataract surgery. (ClinicalTrials.gov number, NCT00431028.).

Intravitreal bevacizumab (Avastin) in combination with verteporfin photodynamic therapy for choroidal neovascularization associated with age-related macular degeneration (IBeVe Study).

BACKGROUND: A novel alternative for combined treatment using verteporfin photodynamic therapy (PDT) has emerged as preliminary safety and efficacy data of the intravitreal use of the anti-angiogenic bevacizumab became available. In the current study we investigate the feasibility of intravitreal bevacizumab combined with verteporfin PDT for the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). METHODS: A single-centre, prospective, open-label study of 11 patients with documented CNV progression after PDT treatment who underwent combined PDT and intravitreal injection of 1.5 mg of bevacizumab was undertaken. Standardized ophthalmic evaluation was performed at baseline and at weeks 1, 2, 12 and 24. Clinical evidence of complications and changes in logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study (ETDRS) charts and in fluorescein leakage from CNV were evaluated. RESULTS: The mean (+/-SD) age of the 11 patients was 74 (+/-5) years. Seven eyes had been treated with one previous PDT session and four eyes had two previous PDT sessions. The mean baseline logMAR ETDRS BCVA was 1.031 (Snellen equivalent, 20/200(-2)). At follow-up weeks 1, 2, 12 and 24, the mean logMAR ETDRS BCVA (Snellen equivalent) was 0.944 (20/160(-2)), 0.924 (20/160(-1)), 0.882 (20/160(+1)), and 0.933 (20/160(-2)), respectively. The change in BCVA from baseline was significant at each study follow-up interval (P < or = 0.001); at 12 and 24 weeks, the mean change in BCVA from baseline was an improvement of 1.49 and of 0.98 ETDRS line, respectively. Fluorescein leakage from CNV was absent in all eyes at week 12. One additional treatment session was required in seven (63.6%) eyes at week 24 due to recurrent fluorescein leakage from CNV ("minimum" [<50% of the leaking area noted at baseline], n = 4; and "moderate" [>50% of the leaking area noted at baseline], n = 3). No progression of the neovascular lesion was observed at week 24. No safety issues were identified throughout the period of the study. CONCLUSIONS: The overall changes in vision and fluorescein leakage from CNV throughout the study suggest that a possible synergistic effect may arise from the combination of intravitreal bevacizumab with verteporfin PDT for the treatment of neovascular AMD.

Comparison of optic disk and retinal nerve fiber layer thickness in nonglaucomatous and glaucomatous patients with high myopia.

PURPOSE: To assess the optic nerve head (ONH) by optical coherence tomography (OCT), confocal scanning laser ophthalmoscopy (CSLO), and the retinal nerve fiber layer (RNFL) by OCT and scanning laser polarimetry (GDx) in highly myopic subjects. DESIGN: Observational cross-sectional study. METHODS: Thirty-five eyes of highly myopic individuals without glaucoma and 17 eyes of highly myopic patients with glaucoma were included in this study. All patients had myopia higher than 5.0 diopters and ocular axial length higher than 25 mm. In those patients without glaucoma, the intraocular pressure (IOP) was less than 21 mm Hg. RESULTS: Mean (SD) OCT cup-to-disk area ratio was 0.45 (0.30) and 0.58 (0.29) in the nonglaucomatous and glaucomatous subjects, respectively (P = .22); CSLO cup-to-disk area ratio was 0.27 (0.27) and 0.24 (0.23), respectively (P = .75); and OCT-RNFL was 65.2 (26.2) microm and 56.8 (28.6) microm (P = .43). CONCLUSIONS: OCT, CSLO, and GDx are not useful to discriminate nonglaucomatous and glaucomatous subjects that have high myopia.

Intravitreal bevacizumab for choroidal neovascularization caused by AMD (IBeNA Study): results of a phase 1 dose-escalation study.

PURPOSE: To evaluate the safety of three dose regimens of intravitreal bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) for the management of choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD). METHODS: This was a prospective, nonrandomized open-label study of 45 patients with AMD and subfoveal CNV. A standardized ophthalmic evaluation was performed at baseline and at weeks 1, 6, and 12 (+/-1) after a single intravitreous injection (1.0, 1.5, or 2.0 mg) of bevacizumab. Main outcomes measures include clinical evidence of toxicity and complications. Changes in best corrected visual acuity (BCVA) and lesion characteristics-macular morphology were also evaluated. RESULTS: The most common adverse events were conjunctival hyperemia and subconjunctival hemorrhage at the injection site. Mean BCVA improved from baseline throughout the study (P < 0.001; ANOVA with Geisser-Greenhouse correction). Compared with baseline, BCVA was improved at week 1 (P = 0.001), week 6 (P < 0.001), and week 12 (P = 0.001; Dunnett test). At week 12, the lesion area and CNV area were stable or decreased in 79.1% (34/43) and in 74.4% (32/43) of patients, respectively, with no deterioration of macular architecture observed in 83.7% (36/43). A dose-related change in BCVA (in Early Treatment Diabetic Retinopathy Study [ETDRS] lines) was observed at week 12 (1.0 mg [+0.3 line]; 1.5 mg [+0.6 line]; and 2.0 mg [+1.0 line]; P = 0.02; nonparametric test for ordered groups). CONCLUSIONS: A single intravitreal bevacizumab injection was well tolerated and, except for minor transient local adverse events, no other adverse events were observed. In the short-term, treatment was associated with vision stabilization or improvement and no unfavorable neovascular lesion-macular changes in most patients.

Retinal assessment using optical coherence tomography.

Over the 15 years since the original description, optical coherence tomography (OCT) has become one of the key diagnostic technologies in the ophthalmic subspecialty areas of retinal diseases and glaucoma. The reason for the widespread adoption of this technology originates from at least two properties of the OCT results: on the one hand, the results are accessible to the non-specialist where microscopic retinal abnormalities are grossly and easily noticeable; on the other hand, results are reproducible and exceedingly quantitative in the hands of the specialist. However, as in any other imaging technique in ophthalmology, some artifacts are expected to occur. Understanding of the basic principles of image acquisition and data processing as well as recognition of OCT limitations are crucial issues to using this equipment with cleverness. Herein, we took a brief look in the past of OCT and have explained the key basic physical principles of this imaging technology. In addition, each of the several steps encompassing a third generation OCT evaluation of retinal tissues has been addressed in details. A comprehensive explanation about next generation OCT systems has also been provided and, to conclude, we have commented on the future directions of this exceptional technique.

Comparison of intravitreal versus posterior sub-Tenon's capsule injection of triamcinolone acetonide for diffuse diabetic macular edema.

PURPOSE: To compare the safety and efficacy of intravitreal versus posterior Sub-Tenon's capsule injection of triamcinolone acetonide for diffuse diabetic macular edema. DESIGN: Prospective, double-masked, randomized controlled trial. PARTICIPANTS: Twelve patients (24 eyes) with bilateral diffuse diabetic macular edema. INTERVENTION: One eye of each patient was randomly assigned to receive a single 4-mg triamcinolone acetonide intravitreal injection and the fellow eye to receive a 40-mg triamcinolone acetonide posterior Sub-Tenon's capsule injection. MAIN OUTCOME MEASURES: Changes in visual acuity and central macular thickness obtained using optical coherence tomography were measured during a 6-month follow-up. Potential treatment complications were monitored, including increases in intraocular pressure (IOP) and cataract progression. RESULTS: Both intravitreal and Sub-Tenon's capsule injections of triamcinolone acetonide resulted in significant but transient improvements in central macular thickness. The mean (+/-standard deviation [SD]) central macular thickness in eyes with intravitreal injection was significantly thinner than in the Sub-Tenon's capsule-injected eyes at 1 month (226.8+/-41.7 microm and 431.5+/-165.8 microm, respectively; P = 0.002) and 3 months (242.3 +/- 93.9 microm and 364.7+/-78.2 microm, respectively; P = 0.005) after triamcinolone acetonide injection. The mean visual acuity (logarithm of the minimum angle of resolution) in the intravitreally injected eyes was significantly better than in the Sub-Tenon's capsule-injected eyes at 3 months post injection (0.832+/-0.293 and 1.107+/-0.339, respectively; P = 0.004). Intraocular pressure did not show any significant difference between the 2 forms of triamcinolone acetonide delivery at any follow-up visit, and no eyes had IOPs >25 mmHg. CONCLUSIONS: The findings from our study neither advocate nor support the use of corticosteroids for the treatment of diabetic macular edema, but do imply that both intravitreal and Sub-Tenon's capsule injections of triamcinolone acetonide may be equally tolerated, with short-term performance clearly favoring the intravitreal (4 mg) more than the SBT capsule (40 mg) route for the anatomic and functional aspects of improvement tested in this investigation.

A single intraoperative sub-Tenon's capsule triamcinolone acetonide injection for the treatment of post-cataract surgery inflammation.

PURPOSE: To compare a single intraoperative sub-Tenon's capsule triamcinolone acetonide injection with steroid drops in the treatment of ocular inflammation after cataract surgery. DESIGN: Randomized, double-masked controlled trial. PARTICIPANTS: A total of 100 patients were randomized prospectively into 2 groups: 50 patients treated with 1% prednisolone eyedrops (control group A) and 50 patients treated with sub-Tenon's capsule triamcinolone (treatment group B). METHODS: All patients underwent phacoemulsification and intraocular posterior lens implantation. After surgery, patients were randomized to receive either (group B) an intraoperative 40 mg triamcinolone acetonide sub-Tenon's capsule injection or (group A) 1% prednisolone acetate eyedrops, according to the following schedule: 1 drop 4 times daily (week 1), 3 times daily (week 2), 2 times daily (week 3), once daily (week 4). To mask the study, group B received vehicle drops administered on a similar schedule, and group A received an intraoperative sub-Tenon's capsule injection of a 1 ml balanced salt solution. MAIN OUTCOME MEASURES: The main outcome measures included inflammation (cell, flare, ciliary flush), intraocular pressure, and lack of response. RESULTS: Triamcinolone was shown to have anti-inflammatory efficacy clinically equivalent to conventional 1% prednisolone eyedrops in reducing intraocular inflammation, as measured by clinical methods. Triamcinolone was found to be as safe as the prednisolone in terms of adverse effects, changes in visual acuity, intraocular pressure, and biomicroscopic and ophthalmoscopic variables. On the third, seventh, fourteenth, and twenty-eighth postoperative days, a significantly lower intraocular pressure (P<0.01) was noted in the triamcinolone group than in the prednisolone group. CONCLUSIONS: A single intraoperative 40-mg triamcinolone acetonide sub-Tenon's capsule injection demonstrated a clinically equivalent therapeutic response and ocular tolerance compared with 1% prednisolone drops in controlling postoperative inflammation after uncomplicated cataract surgery and merits further investigation.