Accuracy of an objective binocular automated phoropter for providing spectacle prescriptions.

CLINICAL RELEVANCE: Currently eye examinations are usually based on autorefraction followed by subjective refraction (SR) with a phoropter. An automated phoropter that can also perform autorefraction may facilitate the optometric workflow. BACKGROUND: The efficiency and feasibility of an objective autorefraction and correction system are assessed by comparing objective refractive measurements with SR on the same subjects and evaluating the visual acuity (VA) values obtained after the objective refractive measurement and correction. METHODS: Objective autorefraction and correction was performed on 41 subjects using an automated binocular phoropter system. The auto-phoropter performs autorefraction by wavefront measurement and corrects the spherical and cylindrical errors with tunable fluidic lenses while the patient looks at a visual display inside the instrument. The instrument outputs are optometric constants of spherical and cylindrical aberrations. After measurement and automated correction of the refractive errors, the VA values were assessed by having the subjects look at an integrated Snellen chart. The objective measurement results were statistically compared with their SR. RESULTS: The correlations between SR and objective autorefraction and correction spherical equivalents (M) were 0.98 (0.97-0.99) and 0.96 (0.93-0.98), the vertical Jackson cross cylinder (J0) were 0.96 (0.92-0.98) and 0.95 (0.91-0.97), and the oblique Jackson cross cylinder (J45) were 0.73 (0.55-0.85) and 0.82 (0.69-0.90), for the right and left eyes, respectively, with the 95% confidence interval (CI) values in parentheses. 89.0% of the 82 eyes had at least 6/7.5 VA. CONCLUSIONS: A significant agreement between the SR and objective autorefraction and correction was observed. An all-objective refractive assessment with instantaneous verification may improve the precision of eye prescriptions and possibly reduce the procedure time.

Performance analysis of a compact auto-phoropter for accessible refractive assessment of the human eye.

We present the performance analysis and specifications of a portable auto-phoropter system that can be employed for fast refractive assessment of a large population. A customized Shack-Hartmann wavefront sensor is developed to accurately measure the defocus and astigmatism of the eye within ±10D and ±6D, respectively. Three fluidic lenses are designed to correct the vision in real time. A digital Snellen chart is integrated into the system to validate the accuracy of the measurement and the correction by means of achieving 20/20 vision. The refractive error of eight subjects (16 eyes) has been measured objectively (without patient's feedback) using the proposed system and the results are compared with their clinical prescription through the Bland-Altman method. It is shown that the auto-phoropter takes less than 8 s to measure and correct the eye refractive error with an accuracy of ±0.25D.

Parametric dog-bone-shaped tunable cylindrical fluidic lens.

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 ${\pm{\rm 5D}}$ 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.

Noninvasive calibrated tissue temperature estimation using backscattered energy of acoustic harmonics.

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.

Real-Time Control of Nanoparticle-Mediated Thermal Therapy Using Photoacoustic Imaging.

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 [Formula: see text] and 0.5 [Formula: see text], 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.

Intracameral dexamethasone injection in the treatment of cataract surgery induced inflammation: design, development, and place in therapy.

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.

Management of cataract in uveitis patients.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.

A new low-cost, compact, auto-phoropter for refractive assessment in developing countries.

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.

CENTRAL SEROUS CHORIORETINOPATHY IN POSTMENOPAUSAL WOMEN RECEIVING EXOGENOUS TESTOSTERONE.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Two Doses of Intravitreal Ziv-Aflibercept versus Bevacizumab in Treatment of Diabetic Macular Edema: A Three-Armed, Double-Blind Randomized Trial.

PURPOSE: 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. DESIGN: Three-armed, double-blind, randomized clinical trial. PARTICIPANTS: Eyes with center-involved DME. METHODS: 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. MAIN OUTCOME MEASURES: Change in best-corrected visual acuity (BCVA) at 12 weeks. RESULTS: 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 BCVA <20/50, the improvement was significantly better at 12 weeks in the ziv-aflibercept 1.25 mg group compared with the IVB group (P = 0.011). CONCLUSIONS: 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 BCVA <20/50. Longer-term efficacy and safety data will be needed to understand the role for this drug in practice.

Visual system manifestations of Alzheimer's disease.

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.

Middle Cerebral Artery, Ophthalmic Artery, and Multibranch Retinal Vessel Occlusion After Cosmetic Autologous Fat Transfer to Forehead.

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.

Intravitreal diclofenac versus intravitreal bevacizumab in naive diabetic macular edema: a randomized double-masked clinical trial.

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.

Mutant Gq/11 promote uveal melanoma tumorigenesis by activating YAP.

Uveal melanoma (UM) is the most common cancer in adult eyes. Approximately 80% of UMs harbor somatic activating mutations in GNAQ or GNA11 (encoding Gq or G11, respectively). Herein, we show in both cell culture and human tumors that cancer-associated Gq/11 mutants activate YAP, a major effector of the Hippo tumor suppressor pathway that is also regulated by G protein-coupled receptor signaling. YAP mediates the oncogenic activity of mutant Gq/11 in UM development, and the YAP inhibitor verteporfin blocks tumor growth of UM cells containing Gq/11 mutations. This study reveals an essential role of the Hippo-YAP pathway in Gq/11-induced tumorigenesis and suggests YAP as a potential drug target for UM patients carrying mutations in GNAQ or GNA11.

Intravitreal bevacizumab injection alone or combined with triamcinolone versus macular photocoagulation in bilateral diabetic macular edema; application of bivariate generalized linear mixed model with asymmetric random effects in a subgroup of a clinical trial.

PURPOSE: To compare the efficacy of intravitreal bevacizumab (IVB) injection alone or with intravitreal triamcinolone acetonide (IVB/IVT) versus macular photocoagulation (MPC) in bilateral diabetic macular edema (DME). METHODS: In this study we revisited data from a subset of subjects previously enrolled in a randomized clinical trial. The original study included 150 eyes randomized to three treatment arms: 1.25 mg IVB alone, combined injection of 1.25 mg IVB and 2 mg IVT, and focal or modified grid MPC. To eliminate the possible effects of systemic confounders, we selected fellow eyes of bilaterally treated subjects who had undergone different treatments; eventually 30 eyes of 15 patients were re-evaluated at baseline, 6, 12, 18, and 24 months. Using mixed model analysis, we compared the treatment protocols regarding visual acuity (VA) and central macular thickness (CMT). RESULTS: Improvement in VA in the IVB group was significantly greater compared to MPC at months 6 and 12 (P = 0.037 and P = 0.035, respectively) but this difference did not persist thereafter up to 24 months. Other levels of VA were comparable at different follow-up intervals (all P > 0.05). The only significant difference in CMT was observed in favor of the IVB group as compared to IVB/IVT group at 24 months (P = 0.048). CONCLUSION: Overall VA was superior in IVB group as compared to MPC up to 12 months. Although the IVB group showed superiority regarding CMT reduction over 24 months as compared to IVB/IVT group, it was comparable to the MPC group through the same period of follow up.

Enhanced depth imaging OCT and indocyanine green angiography changes in acute macular neuroretinopathy.

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.

Spectral-domain optical coherence tomography appearance of a retinal nematode.

A 65-year-old man presented with decreased visual acuity in his left eye of 10 days' duration. Ocular examination revealed visual acuity of 20/200 in the left eye caused by a visible retinal nematode (roundworm) located close to the fovea. Spectral-domain optical coherence tomography imaging showed the nematode in the retinal nerve fiber layer. The patient was followed up without treatment, and the nematode disappeared spontaneously after 5 weeks. Visual acuity in the affected eye improved to 20/25.

Nonmechanical zoom system through pressure-controlled tunable fluidic lenses.

We have developed a variable-power zoom system that incorporates fluidic lenses and has no moving parts. The designed system applies two single-chamber plano-convex fluid singlets, each with their own distinct design, as well as a conventional refractive lens. In this paper, we combine the two fluid elements to form a variable-power telescope, while the fixed lens enables image formation. In this configuration, the image plane location is fixed. By synchronizing the powers of the two fluidic lenses, we produce a varying magnification zoom system. The design of each lens and the coupled system is analyzed. The coupled device experimentally produced a magnification range of 0.1× to 10× zoom or a 20× zoom magnification range with no moving parts. Furthermore, we expand on optical performance and capabilities of our system with fluidic lenses relative to traditional zoom lenses.

Trans-scleral tactile tonometry: an instrumented approach.

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.