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Objective: This work aims to determine whether photoacoustic (PA) thermometry from a commercially available PA imaging system can be used to control the temperature in nanoparticle-mediated thermal therapies. Methods: The PA imaging system was interfaced to obtain PA images while scanning ex-vivo tissue. These images were then used to obtain temperature maps in real-time during heating. Validation and calibration of the PA thermometry were done using a fluoroptic thermometer. This thermometer was also used to develop and tune a software-based proportional integral derivative (PID) controller. Finally, a PA-based PID closed-loop controller was used to control gold nanorod (GNR) mediated laser therapy. Results: The use of GNRs substantially enhanced laser heating; the temperature rise increased 7-fold by injecting a GNR solution with a concentration of 0.029 mg/mL. The control experiments showed that the desired temperature could be achieved and maintained at a targeted location in the ex-vivo tissue. The steady-state mean absolute deviations (MAD) from the targeted temperature during control were between 0.16 $^\circ {\kern-0.70007pt}\text{C}$ and 0.5 $^\circ {\kern-0.70007pt}\text{C}$ , depending on the experiment. Conclusion: It was possible to control hyperthermia treatments using a software-based PID controller and a commercial PA imaging system. Significance: The monitoring and control of the temperature in thermal-based therapies are important for assuring a prescribed temperature to the target tissue while minimizing the temperature of the surrounding healthy tissue. This easily implemented non-invasive control system will facilitate the realization of a broad range of hyperthermia treatments.

This chapter comprehensively covers all aspects of endogenous endophthalmitis from systemic infectious agents, with an emphasis on reported and newer etiologies to broaden the diagnostic and investigative acumen of treating ophthalmic providers. The discussion includes the etiology of metastatic endophthalmitis and diagnostic investigations, including polymerase chain reaction (PCR), for identification of bacterial and viral infections involving the eye in both immunosuppressed in non-immunosuppressed patients. Additionally, we present clinical and diagnostic findings of fungal infections, protozoal infections, and helminthic infections. Pediatric cases are also reported and etiologies described. We discuss both etiology and diagnostic challenges. Current therapeutic modalities and outcomes are reviewed. While no two cases of metastatic endophthalmitis are the same, some similarities may exist that allow us to generalize how to approach and treat this potentially sight- and life-threatening spectrum of diseases and find the underlying systemic cause.

A real-time and non-invasive thermometry method is crucial for thermal therapies to monitor and control the treatment. Ultrasound can be used as an attractive thermometry modality for its relatively high sensitivity to change in temperature and fast data collection and processing abilities. In this work, an ultrasound thermometry method based on the change in backscattered energy (CBE) is used to control the tissue temperature using a closed-loop controller in real-time. A clinical high-frequency ultrasound scanner was used to acquire RF echo data from ex vivo porcine tissue samples while the tissue was being exposed to an interstitial laser heating source. The control system was used to rapidly increase the temperature from 37°C (baseline temperature) to 43 °C (target temperature) and maintain the target temperature for about 6 minutes. The results show that the ultrasound thermometry based on CBE generated by a high-frequency ultrasound scanner can be used to generate 2D temperature maps of a localized heating region in the hyperthermia temperature range (∼43°C). The estimated temperature varied by an average of ±0.8 °C compared to a calibrated fiber-optic measurement. Thus, a non-invasive ultrasound thermometry method based on the CBE technique can be used for real-time monitoring and control of hyperthermia treatments, using the interstitial laser heating source with acceptable accuracy.

Tunable spherical fluidic lenses are among the most essential components in adaptive optics. However, fabricating cylindrical tunable lenses has proven more challenging, mainly due to the difficulty in eliminating the defocus component. We demonstrate a parametric approach to minimize the defocus in cylindrical tunable fluidic lenses. We theoretically model and experimentally verify that a dog-bone-shaped tunable cylindrical fluidic lens exhibits almost pure cylindrical performance within the range of ± 5 D of astigmatism. We anticipate these results will facilitate the use of tunable cylindrical fluidic lenses in adaptive optics applications and particularly ophthalmic devices, where rapid and reliable wavefront correction is required.

We describe an automated phoropter employing fluidic lenses, measuring the visual acuity and correcting the vision without patient feedback within seconds. The

Purpose A real-time and non-invasive thermometry technique is essential in thermal therapies to monitor and control the treatment. Ultrasound is an attractive thermometry modality due to its relatively high sensitivity to change in temperature and fast data acquisition and processing capabilities. A temperature-sensitive acoustic parameter is required for ultrasound thermometry in order to track the changes in that parameter during the treatment. Currently, the main ultrasound thermometry methods are based on variation in the attenuation coefficient, the change in backscattered energy of the signal (CBE), the backscattered radio-frequency (RF) echo-shift due to change in the speed of sound and thermal expansion of the medium, and change in the amplitudes of the acoustic harmonics. In this work, an ultrasound thermometry method based on second harmonic CBE (CBEh2) and combined fundamental and second harmonic CBE (CBEcomb) is used to produce 2D temperature maps, detect localized heated region generated by low intensity focused ultrasound (LIFU), and control temperature in the heated region. Materials and methods Ex vivo pork muscle tissue samples were exposed to localized LIFU heating source and 2D temperature maps were produced from the RF data acquired by a 4.2 MHz linear array probe using a Verasonics Vantage™ ultrasound scanner (Verasonics Inc., Redmond, WA) after the exposure. Calibrated needle thermocouples were also placed in the ex vivo tissue sample close to the LIFU focal zone for temperature calibration purposes. The estimated temperature maps were the established echo-shift technique. A tissue motion compensation algorithm was also used to reduce the susceptibility to motion artifacts. Results 2D temperature maps were generated using CBE of acoustic harmonic and echo-shift techniques. The results show a direct correlation between the CBE of acoustic harmonics and focal tissue temperature for a range of temperatures from 37 °C (baseline) to 47 °C. Conclusions The findings of this study show that the CBE of acoustic harmonics technique can be used to noninvasively estimate temperature change in tissue in the hyperthermia temperature range.

Cataract surgery is one of the most commonly performed surgeries worldwide, with nearly 20 million cases annually. Appropriate prophylaxis after cataract surgery can contribute to a safe and quick visual recovery with high patient satisfaction. Despite being the current standard of care, the use of multiple postoperative eye drops can create a significant burden on these patients, contributing to documented and significant non-adherence to the postoperative regimen. Over the past 25 years, there have been a few studies analyzing the use of intracameral dexamethasone (DXM) in controlling inflammation following cataract surgery. This review explores various drug delivery approaches for managing intraocular inflammation after cataract surgery, documenting the strengths and weaknesses of these options and examining the role of intracameral DXM (among these other strategies) in controlling postoperative intraocular inflammation. Intracameral DXM has a particular advantage over topical steroids in possibly decreasing postoperative inflammatory symptoms and objective anterior cell and flare scores. Compared to topical steroids, there may be a slightly less theoretical risk of significant intraocular pressure spikes and systemic absorption. In addition, surveys indicate patients prefer an intraoperative intracameral injection over a self-administered postoperative eye drop regimen. However, there are several adverse effects associated with intracameral DXM delivery that are not seen with the noninvasive topical approach. Although it is unlikely that intracameral DXM will replace topical medications as the standard management for postoperative inflammation, it is seemingly another safe and effective strategy for controlling postoperative inflammation after routine cataract surgery.

To compare the efficacy of 2 doses of intravitreal ziv-aflibercept (IVZ) with intravitreal bevacizumab (IVB) in the treatment of center-involved diabetic macular edema (DME) at 12 weeks.Three-armed, double-blind, randomized clinical trial.Eyes with center-involved DME.In this trial, 123 eyes with DME were randomly assigned to 3 injections of 1.25 mg IVZ, 2.5 mg IVZ, and 1.25 mg IVB every 4 weeks. Complete ophthalmologic examination and central macular thickness (CMT) measurement by optical coherence tomography were performed every 4 weeks up to 12 weeks.Change in best-corrected visual acuity (BCVA) at 12 weeks.Although no significant difference was evident between the 2 ziv-aflibercept groups at 12 weeks, the BCVA change was significantly better in the ziv-aflibercept 1.25 mg group than in the IVB group at the 12-week visit (P = 0.021). In regard to CMT changes, there was no significant difference between the 2 ziv-aflibercept groups; however, a significantly greater reduction in CMT was observed in the ziv-aflibercept 2.5 mg group compared with the IVB group at 12 weeks (P = 0.037). Subgroup analysis disclosed no difference in BCVA outcomes at 12 weeks among the groups in the eyes with baseline BCVA ≥20/50. In the eyes with baseline BCVA20/50, the improvement was significantly better at 12 weeks in the ziv-aflibercept 1.25 mg group compared with the IVB group (P = 0.011).The 12-week results of this trial disclosed that both 1.25 mg and 2.5 mg doses of IVZ and IVB demonstrated BCVA improvement over baseline in the treatment of center-involved DME. However, a stronger effect of IVZ compared with IVB in terms of both visual acuity improvement and macular thickness reduction was detected in the eyes with initial BCVA20/50. Longer-term efficacy and safety data will be needed to understand the role for this drug in practice.

A 65-year-old woman with left hemiparesis and sudden loss of visual acuity in her right eye presented a few hours after cosmetic injection of autologous fat to her forehead. Right eye visual acuity was no light perception. Funduscopy revealed widespread retinal whitening and multibranch retinal vessel occlusion. Fluorescein angiography showed markedly delayed choroidal and retinal filling together with occlusion of multiple branches of retinal arteries and veins. On magnetic resonance imaging of the brain, multiple lesions compatible with recent infarction were detected. The authors diagnosed multibranch retinal artery and vein occlusion in the right ophthalmic and middle cerebral arteries due to fat emboli. This case emphasizes the need to reevaluate the safety of such aesthetic procedures, particularly in the facial zone to prevent devastating complications. [ Ophthalmic Surg Lasers Imaging Retina . 2015;46:593–596.]

This review is timely because the outcomes of surgical invention in uveitic eyes with cataract can be optimized with adherence to strict anti-inflammatory principles.All eyes should be free of any cell/ flare for a minimum of 3 months preoperatively. Another helpful maneuver is to place dexamethasone in the infusion fluid or triamcinolone intracamerally at the end of surgery. Recent reports about the choice of intraocular lens material or lens design are germane to the best surgical outcome. Integrating these findings will promote better visual outcomes and allow advancement in research to further refine these surgical interventions in high-risk uveitic eyes.Control of inflammation has been shown to greatly improve postoperative outcomes in patients with uveitis. Despite better outcomes, more scientific research needs to be done regarding lens placement and materials and further research needs to adhere to the standardized reporting of uveitis nomenclature. Future studies should improve postoperative outcomes in eyes with uveitis so that they approach those of eyes undergoing routine cataract procedures.

Using a phoropter to measure the refractive error is one of the most commonly used methods by ophthalmologists and optometrists. Here, we demonstrate design and fabrication of a portable automatic phoropter with no need for patient’s feedback. The system is based on three tunable-focus fluidic lenses and thin-film holographic optical elements to perform automatic refractive error measurement and provide a diagnostic prescription without supervision. Three separate lenses are deployed to correct the defocus and astigmatism. The refractive error is measured using a Shack-Hartmann wavefront sensor that calculates the Zernike values of an infrared wavefront emerging from the eye. Holographic optical elements steer the emerging wavefront into the wavefront sensor, while simultaneously providing an unobstructed view for the subject. The power of each lens is controlled by pumping a liquid in and out of the lens chamber using servo motor actuated diaphragm pumps. Spherical and cylindrical correction range of −10 to +10 diopters with 0.1 diopter increments is achieved in less than 15 seconds using wavefront sensor feedback to the pumps. This system can be used in rapid screening of large patient populations especially in the developing countries that lack sufficient facilities and specialist doctors.

Phoropters are the most common instrument used to detect refractive errors. During a refractive exam, lenses are flipped in front of the patient who looks at the eye chart and tries to read the symbols. The procedure is fully dependent on the cooperation of the patient to read the eye chart, provides only a subjective measurement of visual acuity, and can at best provide a rough estimate of the patient’s vision. Phoropters are difficult to use for mass screenings requiring a skilled examiner, and it is hard to screen young children and the elderly etc. We have developed a simplified, lightweight automatic phoropter that can measure the optical error of the eye objectively without requiring the patient’s input. The automatic holographic adaptive phoropter is based on a Shack-Hartmann wave front sensor and three computercontrolled fluidic lenses. The fluidic lens system is designed to be able to provide power and astigmatic corrections over a large range of corrections without the need for verbal feedback from the patient in less than 20 seconds.

Retinal diseases such as Age-Related Macular Degeneration (ARMD) affect nearly one in three elderly patients. ARMD damages the central vision photoreceptors in the fovea. The Photostress Test is a simple technique for testing for the early effects of ARMD. Here, the illumination sources in a novel self-administered Photostress Testing device were modeled for safety and distribution in illumination software. After satisfying the design constraints in the model, a prototype of the illumination system was fabricated and tested to confirm the modeling results. The resultant prototype can be used to aid in the diagnosis of retinal disease and is well within retinal safety levels.

The purpose of the study is to compare single injection of intravitreal diclofenac (IVD) with intravitreal bevacizumab (IVB) in the treatment of eyes with naïve diabetic macular edema (DME). In this randomized clinical trial, 57 eyes of 57 patients were randomly assigned to IVD group (30 eyes), cases who received a single intravitreal injection of diclofenac (500 μg/0.1 ml), and IVB group (27 eyes), cases who received a single intravitreal injection of bevacizumab (1.25 mg). Change in best-corrected visual acuity in logMAR at week 12 was the primary outcome measure. Secondary outcomes included changes in central macular thickness, macular leakage, and potential injection-related complications. Best-corrected visual acuity improved significantly more in the IVD group than in the IVB group (P = 0.033), from 0.57 ± 0.25 to 0.49 ± 0.31 versus 0.55 ± 0.24-0.59 ± 0.27 logMAR at 12 weeks, respectively. However, the difference of macular thickness changes was in favor of IVB, but not to a significant level. The amount of change in leakage was not significantly different between the groups either. None of the eyes, in either group, developed ocular hypertension (≥23 mmHg) or cataract progression. No important injection-related complication was observed during the study period. This study demonstrated the superiority of IVD over IVB in the treatment of naïve DME regarding functional, but not anatomical outcomes. Therefore, using IVD as an adjunct or even alternative to other treatments might enhance the functional outcomes in such cases. Further studies are warranted to confirm potential benefit of IVD observed in this study.

The authors describe indocyanine green angiography (ICGA) and enhanced depth imaging optical coherence tomography (EDI-OCT) in a 46-year-old male patient with acute macular neuroretinopathy (AMN). The chief complaint was decreasing visual acuity and metamorphopsia in both eyes of 1-month duration. Visual field assessment, fluorescein angiography, OCT, ICGA, and EDI-OCT were performed initially and at 3 months. ICGA showed choroidal vascular hyperpermeability and punctuate choroidal hyperfluorescent spots, especially in the left eye. EDI-OCT showed increased choroidal macular thickness, with inner and outer retinal layers affected. EDI-OCT and ICGA reveal that both the choroid and retina can be affected in AMN; however, the primary pathology and localization of depth of involvement in AMN remains unclear.

This article describes a feasibility study of a novel trans-scleral tonometer based on the use of an instrumented form of digital palpation tonometry. Similar to manual digital palpation tonometery, trans-scleral tonometer utilizes two force probes offset by a fixed distance. Force indentation data from these probes have been shown to correlate with the intraocular pressure (IOP) of the eye. Enucleated porcine eyes were used to experimentally validate the approach. The observed hysteresis in the force data was analyzed using an analytical model that accounts for the outflow of the aqueous humor. The predictions of the model indicate that the primary reason behind the observed hysteresis is stress relaxation (accommodation) in the visco-elastic corneo-scleral shell. Experimental data from eye distention and indentation tests were then used to infer the conditions under which the novel tonometer would be expected to have an accuracy of ±1 mmHg. Analysis of the data shows that indentation rates should be kept below 0.5 mm/s for a pressure range of 10-35 mmHg. Two commonly used pressure control protocols were tested in an effort to ensure accurate IOP values during the palpation tests. Due to the large increase of IOP during digital palpation, the trans-scleral (intra-vitreous) pressurization was found to be inadequate, leading to clogging of the line by the displaced vitreous. No such problems were identified when the eye was pressurized through the cornea and into the anterior chamber. Force data from multiple palpation experiments are used to generate calibration curves for a two-probe conceptual tonometer. The calibration showed that a 10 mN of force variation corresponds to 1 mmHg of IOP change. A possible implementation using a contoured facial mask is also presented.

Alzheimer's disease (AD) is an increasingly common disease with massive personal and economic costs. While it has long been known that AD impacts the visual system, there has recently been an increased focus on understanding both pathophysiological mechanisms that may be shared between the eye and brain and how related biomarkers could be useful for AD diagnosis. Here, were review pertinent cellular and molecular mechanisms of AD pathophysiology, the presence of AD pathology in the visual system, associated functional changes, and potential development of diagnostic tools based on the visual system. Additionally, we discuss links between AD and visual disorders, including possible pathophysiological mechanisms and their relevance for improving our understanding of AD.

Central serous chorioretinopathy (CSR) is a serous detachment of the neurosensory retina commonly associated with male sex, Type-A personality and corticosteroid use. Exogenous administration of androgens and development of CSR in men has been reported. Only one case of CSR in a postmenopausal woman receiving exogenous androgen therapy has been reported. The authors describe three cases of chronic CSR in postmenopausal women receiving exogenous testosterone therapy.Diagnosis was based on characteristic clinical, fluorescein angiographic, and optical coherence tomography findings. The three women were being treated with exogenous testosterone and progesterone therapy for symptoms of menopause and libido loss.Average age at presentation was 54.7 years (53-56 years), average duration of exogenous androgen use was 61 months (36-87 months), with average 19.7-month follow-up. Resolution of symptoms seemed correlated with cessation of androgen use despite treatment with oscillatory photodynamic therapy and intravitreal pharmacotherapy with antivascular endothelial growth factor agents.Exogenous testosterone is increasingly prescribed for menopausal symptoms and libido loss. Treatment with oscillatory photodynamic therapy, supplemental bevacizumab intravitreal pharmacotherapy, and cessation of exogenous androgen therapy was successful in three cases of chronic, therapy-resistant CSR. Ophthalmologists should inquire about androgen usage in patients who present with CSR, especially in the setting of therapy resistance.

The purpose of this study was to report the 24-month findings of a randomized clinical trial comparing intravitreal bevacizumab (IVB) injection alone or in combination with intravitreal triamcinolone acetonide (IVT) versus macular laser photocoagulation (MPC) as a primary treatment for diabetic macular edema.The eyes were randomly assigned to 1 of the 3 study arms: the IVB group, patients who received 1.25 mg IVB; the IVB/IVT group, patients who received 1.25 mg of IVB and 2 mg of IVT; and the MPC group, patients who underwent focal or modified grid laser. Of 150 eyes (50 in each group) in the primary trial, 123, 119, and 113 eyes completed follow-ups at 12, 18, and 24 months, respectively. A total of 39 (78%), 36 (72%), and 38 (76%) eyes in the IVB, IVB/IVT, and MPC groups remained in the study within 24 months, respectively. Retreatment was performed at 3-month intervals whenever indicated. Data from a 24-month follow-up are presented. Changes in best-corrected visual acuity and central macular thickness up to 24 months were the main outcome measures in this study.Retreatment was required in 37 (94.9%), 27 (75.0%), and 31 (81.6%) eyes, respectively, in the IVB, IVB/IVT, and MPC groups up to 24 months. The significant superiority of visual acuity improvement in the IVB group, which had been noted at Month 6, did not sustain thereafter up to 24 months, and the difference among the groups was not significant at all visits. However, the mean visual acuity improvement was greater in the IVB group than the other groups and in the IVB/IVT group compared with the MPC group. The reduction of central macular thickness was more in the IVB group in relation to the other two treatment groups; however, the difference among the groups was not statistically significant at any of the follow-up visits.In terms of vision improvement, the significant superiority of the IVB over the combined IVB/IVT and MPC treatment that had been observed at Month 6 did not sustain up to 24 months. This means that although IVB treatment may be a better choice than two other options in short term, the magnitude of this beneficial effect diminishes over time.

PURPOSE: To investigate the effect of blunt foreign body impact on a human cornea after photorefractive keratectomy (PRK) and LASIK using a simulation model. METHODS: Computational simulations were performed using a finite element analysis program (LS-Dyna, Livermore Software Technology Corp). The blunt foreign body was set to impact at the center of the corneal surface models (after PRK and LASIK) with thicknesses of 500, 450, 400, 350, and 300 μm. Corneal rupture was assumed to occur at a peak stress of 9.45 MPa and at a strain of 18%. The foreign body projectile was blunt in shape, made from aluminum, contained plastic-kinematic properties, and had a density of 2700 kg/m 3 . RESULTS: The projectile was launched at the center of the cornea with velocities ranging from 20 to 60 m/s. The threshold of impact velocities creating rupture in corneal thicknesses of 500, 450, 400, 350, and 300 μm were 33, 32.8, 30.7, 27.9, and 22.8 m/s, respectively, in the PRK model. In the LASIK model, the thresholds creating rupture in the stromal bed of the corneas with thicknesses of 500, 450, 400, 350, and 300 μm were 40, 38.1, 35.6, 31.5, and 26.7 m/s, respectively. The 110-μm corneal flap in the LASIK model ruptured at all velocities. CONCLUSIONS: Ruptures occurred at lower velocities in the PRK cornea model than in the corneal stromal bed of the LASIK model following blunt foreign body impact.

We demonstrate a variable focal length achromatic lens that consists of a flat liquid crystal diffractive lens and a pressure-controlled fluidic refractive lens. The diffractive lens is composed of a flat binary Fresnel zone structure and a thin liquid crystal layer, producing high efficiency and millisecond switching times while applying a low ac voltage input. The focusing power of the diffractive lens is adjusted by electrically modifying the sub-zones and re-establishing phase wrapping points. The refractive lens includes a fluid chamber with a flat glass surface and an opposing elastic polydimethylsiloxane (PDMS) membrane surface. Inserting fluid volume through a pump system into the clear aperture region alters the membrane curvature and adjusts the refractive lens’ focal position. Primary chromatic aberration is remarkably reduced through the coupling of the fluidic and diffractive lenses at selected focal lengths. Potential applications include miniature color imaging systems, medical and ophthalmic devices, or any design that utilizes variable focal length achromats.

Purpose We prospectively evaluated a new treatment for recalcitrant choroidal neovascularization (CNV) in 4 patients. We used an infrared laser (810 nm) in oscillatory thermotherapy (OTT) mode combined with indocyanine green (ICG) dye, utilizing the beneficial effect of both thermotherapy and photodynamic therapy. We describe preliminary experiences with ICG-assisted OTT (I-OTT) combined with intravitreal bevacizumab/dexamethasone for refractory peripapillary CNV resistant to standard therapy. Methods Clinical examination, funduscopy, fluorescein angiography, and optical coherence tomography were performed at baseline and postoperatively. Infrared laser spot size was approximately one-half the lesion size (oscillation 2-3 Hz). Intravitreal injections of bevacizumab (1.25 mg) and dexamethasone (1000 µg) were done during the same visit. Results Mean follow-up was 12.5 months (range 5-17). Mean energy level was 325 mW (range 200-500) in oscillatory mode (2-3 Hz/sec) pre- and post-ICG infusion. Indocyanine green dose was approximately 1 mg/kg (75 mg/patient). All patients had a single treatment. Mean visual acuity improved in 1 patient from 20/60 to 20/30 and remained the same in the other 3 (20/20, 20/40, and 20/400). At final examination, there was no evidence of clinical or angiographic activity of CNV. Conclusions Indocyanine green-assisted OTT has the potential to treat CNV in wet age-related macular degeneration. It may reduce thermal side effects and eliminate or reduce the need for frequent intravitreal treatment. We postulate that I-OTT has a synergistic effect of thermal energy combined with a weak photosensitizer (ICG) applied in an individualized manner, which minimizes thermal damage to retinal and choroidal tissue. Additional anti-vascular endothelial growth factor pharmacotherapy enhances the effect of I-OTT on abnormal new vessels.

Purpose To evaluate the safety and effect of combined intravitreal methotrexate and bevacizumab on choroidal neovascularization in age-related macular degeneration (AMD). Methods Seven eyes of 7 patients (4 female; mean age 65.43±5.96 years) with choroidal neovascularization secondary to AMD were studied. Patients received intravitreal injection of methotrexate and bevacizumab and were examined every 1.5 months. Reinjections were performed with bevacizumab only. Results Three patients had 3 months, 3 had 4.5 months, and 1 had 8 months of follow-up. Mean number of reinjections was 2.0. In all patients, best-corrected visual acuity (BCVA) improved compared to baseline. Central macular thickness (CMT) decreased in all but one patient who had no reduced visual acuity. Mean BCVA (logMAR) was 1.27±0.43 D at baseline, 1.1 ±0.38 D at week 6, and 0.93±0.31 D at month 3. Mean BCVA in 3 patients at 4.5 months was 1.1±0.15 D. There were statistically significant differences between BCVA before injection and at week 6 (p=0.017), 3 months (p=0.005), and 4.5 months (p=0.04). Mean baseline CMT was 389±177 μm, 371±154 μm at 6 weeks, and 317±108 μm at 3 months. Mean CMT in 3 patients at 4.5 months was 266±66 μm. There were no statistically significant differences between baseline CMT and after treatment. No scar formation, increase of scar, or adverse reaction to methotrexate injection were seen. Conclusions Addition of intravitreal methotrexate to bevacizumab was safe in 7 eyes of 7 patients. It may enhance the therapeutic effect in regression of neovascularization in AMD and may reduce development of a fibrous component and disciform scar formation.

Purpose: To describe an unusual case of idiopathic retinal vasculitis, aneurysms, and neuroretinitis syndrome associated with a positive perinuclear antineutrophil cytoplasmic antibody test. Methods: This is an interventional case report. A 22-year-old man with decreased vision underwent ophthalmoscopic, angiographic, and laboratory evaluation. The left eye underwent laser therapy due to circinate retinopathy and more severe involvement. Results: Extensive systemic workup was negative. The only positive laboratory test was a positive perinuclear antineutrophil cytoplasmic antibody (1/40 dilution) detected by indirect immunofluorescence and enzyme-linked immunosorbent assay (positive for antimyeloperoxidase antibody). The patient was observed for 2 years. The disorder remained limited to the eyes, and further systemic workup was unrevealing; perinuclear antineutrophil cytoplasmic antibody titer remained positive. Vision remained stable in the treated eye and was slightly reduced in the untreated eye. Conclusion: Idiopathic retinal vasculitis, aneurysms, and neuroretinitis syndrome may be suggestive of a retinal form of perinuclear antineutrophil cytoplasmic antibody–associated vasculitis.

After evaluating experimentally the diffusion processes in the retina using peroxidase as a tracer material (previously published work), we found that junctional complexes of the retinal pigment epithelium and retinal capillaries were the major impediment to free diffusion between the retina and choroidal-retinal blood vessels. These experiments indicated that to achieve high therapeutic concentrations of medications inside the eye, it was necessary to administer them by intravitreal injection. Soon after initial experimental work the necessity of combining antibiotics or antibiotics with steroids became obvious. As the use of intravitreal injection grew over the last 2 decades, so did the concept of combination therapy.This review describes potential causes of drug-drug interaction and the rationale for combination therapy when injected into the vitreous cavity, encompassing publications between 1971 and 2008.We describe the conditions that can cause physical-chemical interactions between the medications and the need for combination therapy for treatment of various intraocular disease processes.The intravitreal injection of medication and their combinations has become a part of standard care for many diseases of the retina and choroid. This article reviews the potential interaction of nontoxic doses of medications when injected simultaneously in the vitreous cavity, and disease processes that are now treated with these combination therapies.

Background Intravitreal injection (IVI) with administration of various pharmacological agents is a mainstay of treatment in ophthalmology for endopthalmitis, viral retinitis, age-related macular degeneration, cystoid macular edema, diabetic retinopathy, uveitis, vascular occlusions, and retinal detachment. The indications and therapeutic agents are reviewed in this study. Methods A search of the English, German, and Spanish language MEDLINE database was conducted. A total of 654 references spanning the period through early 2008 were individually evaluated. Results The advantage of the IVI technique is the ability to maximize intraocular levels of medications and to avoid the toxicities associated with systemic treatment. Intravitreal injection has been used to deliver several types of pharmacological agents into the vitreous cavity: antiinfective and antiinflammatory medications, immunomodulators, anticancer agents, gas, antivascular endothelial growth factor, and several others. The goal of this review is to provide a detailed description of the properties of numerous therapeutic agents that can be delivered through IVI, potential complications of the technique, and recommendations to avoid side effects. Conclusion The IVI technique is a valuable tool that can be tailored to the disease process of interest based on the pharmacological agent selected. This review provides the reader with a comprehensive summary of the IVI technique and its multitude of uses.

Fifteen patients underwent a pars plana approach vitrectomy and membranectomy after acute and chronic injury. In all cases the lens fragments, hemorrhage, and secondary membranes were removed restoring clarity to the ocular media. In two cases the final visual acuity was limited by pre-existing retinal injury. The advantages of pars plana approach are the small incision and minimal ocular manipulation during surgery. In the presence of retinal injury, diathermy during the procedure or photocoagulation within 24 hours is also indicated.

We evaluated the effects of argon-green (514.5 nm) and CW neodymium YAG (1060 nm) wavelengths on experimentally detached retinas of primates. Neither laser produced damage to the sensory retina of the fovea. The argon green wavelength, which was absorbed by haemoglobin in the vessel or by extravasated red blood cells, created vasospasm and nerve fiber layer damage. The beam of the CW YAG was not absorbed by haemoglobin; therefore, no vasospasm could be produced on experimentally detached retinas.

To evaluate the clinical features and functional and anatomical outcomes after surgical intervention in pediatric rhegmatogenous retinal detachment.In this retrospective case series, pediatric patients with rhegmatogenous retinal detachment who had surgical intervention were included. Cases were categorized into five main etiology groups: congenital or developmental (48 eyes); trauma (54 eyes); myopia alone (12 eyes); previous intraocular surgery (10 eyes); and miscellaneous (3 eyes). Patients' demographic, clinical, and surgical outcomes, as well as fellow eye findings were evaluated.One hundred twenty-seven eyes of 108 patients (mean age: 12.1 +/- 4.1 year, 80.6% male) were included. Scleral buckling was the initial procedure in 31% of eyes and vitrectomy in 63%. Mean follow-up was 34 +/- 21 months (median 33 months). Retinal reattachment at last follow-up was achieved in 74.9% of eyes. Visual acuity was/=20/200 in 14% of eyes preoperatively and in 47.9% of eyes at final follow-up (P = 0.001). Retinal pathologies (mostly lattice degeneration) were noted in 82.2% of fellow eyes.Trauma and congenital-developmental anomalies were the leading etiologies in pediatric rhegmatogenous retinal detachment in this review. Despite the complexity of rhegmatogenous retinal detachment and presence of vision-threatening anomalies, anatomic and functional outcomes were acceptable. Regular ophthalmoscopy of the sound eye is recommended for children at risk.

PURPOSE: To evaluate retinal toxicity of varying doses of rapamycin when injected intravitreally in rabbits. Rapamycin is a potent immunosuppressive agent with significant antitumor and antiangiogenic properties, clinically approved for prevention of organ transplant rejection. METHODS: Twelve New Zealand albino rabbits were divided into four groups. Four different doses of rapamycin were prepared in 0.1 ml: 20 µg, 50 µg, 200 µg, and 1000 µg. Each concentration was injected in one eye of three rabbits, and 0.1 ml volume of sterile BSS was injected into the contralateral eye of the three rabbits. Slit-lamp and fundoscopic examinations were performed and the animals were observed for 2 weeks for signs of infection, inflammation, and toxicity. A baseline ERG was performed before drug treatment and at day 14, after which the rabbits were euthanized. Histology of the enucleated eyes was studied to look for retinal toxicity. RESULTS: ERG results showed some decrease in scotopic response; however this was not dose related. ERG results were normal at 20 µg. Histological results showed no retinal toxicity in all groups. CONCLUSION: Although ERG changes were identified at dosages between 50-1000 µg, the histology of all groups up to 1000 µg did not show any discernable abnormalities.OBJETIVO: Avaliar a toxicidade da injeção intravítrea de diferentes doses de rapamicina para a retina de coelhos. Rapamicina é uma potente droga imunossupressora aprovada clinicamente para a prevenção da rejeição de transplantes de orgãos. MÉTODOS: Doze coelhos albinos da Nova Zelândia foram usados neste estudo. Foram divididos em quatro grupos. Quatro diferentes doses de rapamicina foram preparadas nas seguintes concentrações: 20 µg, 50 µg, 200 µg, 1000 µg. Foram realizadas injeções intravítreas de 0,1 ml de cada concentração em um olho de três coelhos e 0,1 ml de solução salina foi injetada no olho contralateral de cada coelho. Foram realizadas biomicroscopia e fundoscopia e observamos sinais de inflamação, infecção ou toxicidade durante duas semanas. Fizemos um ERG antes do tratamento e outro 14 dias depois da injeção intravítrea. Os animais foram sacrificados, fizemos a enucleação dos olhos e preparamos o tecido para a avaliação histológica. RESULTADOS: Os resultados do ERG e da histologia demonstraram diminuição da resposta escotópica, entretanto essa diminuiç&atildeão foi dose dependente. A histologia foi normal em todos os grupos. CONCLUSÃO: A injeção intravítrea de rapamicina levou a alterações eletrorretinográficas nos grupos de 50-1000 µg, entretanto a histologia foi normal em todos os grupos até 1000 µg.

PURPOSE To report visual outcomes and complication rates associated with one-stage surgery for the management of uveitic cataract associated with posterior segment disease. METHODS In this interventional case series, 19 eyes (19 patients) with posterior segment involvement due to chronic uveitis underwent sutureless scleral tunnel incision phacoemulsification combined with total vitrectomy using 25-gauge instruments and posterior chamber intraocular lens (PC-IOL) implantation. Membrane peeling and endolaser photocoagulation were performed when indicated. Outcome measures were visual acuity, inflammatory activity, macular edema, and complications of surgery. RESULTS After a minimum 12-month follow-up, visual acuity was >or=20/100 in 12 eyes (63.2%); 6 eyes (31.6%) had visual acuity of >or=20/40. A decrease in postoperative inflammatory activity of 1 grade was observed in 8 eyes (42.1%). Sixteen eyes had cystoid macular edema before surgery; and 12 eyes had cystoid macular edema after surgery. Early postoperative complications included the following: transient corneal edema, 10 eyes (50.3%); fibrin reaction, 3 eyes (15.8%), and posterior synechiae, 9 eyes (47.3%). Glaucoma was the most common late postoperative complication (3 eyes [18.8%]). Nine eyes (47.4%) needed YAG laser capsulotomy during the first year. CONCLUSION Sutureless combined 25-gauge total vitrectomy, phacoemulsification, and PC-IOL implantation may be well tolerated with an acceptable complication rate for selected uveitic eyes with significant cataract and coexisting posterior segment disease for restoring useful vision.