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.

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.

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.

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.

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.

Finite element analysis of blunt foreign body impact on the cornea after PRK and LASIK.

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.

Two-year results of a randomized trial of intravitreal bevacizumab alone or combined with triamcinolone versus laser in diabetic macular edema.

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

Randomized trial of intravitreal clindamycin and dexamethasone versus pyrimethamine, sulfadiazine, and prednisolone in treatment of ocular toxoplasmosis.

PURPOSE: To compare the efficacy of intravitreal injection of clindamycin and dexamethasone with classic treatment for ocular toxoplasmosis. DESIGN: Prospective, randomized single-masked clinical trial. PARTICIPANTS: A total of 68 patients with active ocular toxoplasmosis were assigned randomly to 2 treatment groups: 34 in the intravitreal clindamycin plus dexamethasone (IVCD) group and 34 in the classic treatment (CT) group. INTERVENTION: The IVCD group received 1 to 3 injection(s) of 1 mg intravitreal clindamycin and 400 µg dexamethasone, and the CT group received 6 weeks of treatment with pyrimethamine and sulfadiazine plus prednisolone. Antitoxoplasmosis antibodies (immunoglobulin [Ig] M and IgG) were measured using an enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Changes in retinochoroidal lesion size, measured by a computer program written in the MATLAB environment, 6 weeks after initiation of treatment. Visual acuity (VA) changes, vitreous inflammatory response, adverse drug reactions, and rate of recurrence were secondary outcome measures. RESULTS: The mean number of injections in the IVCD group was 1.6. The lesion size reduction was statistically significant after treatment in both IVCD and CT groups (P < 0.001 and P = 0.009, respectively). However, the difference in mean percentage of reduction at 6 weeks was not significant: 57.0 ± 27.8% in the IVCD group versus 58.4 ± 29.3% in the CT group (P = 0.569). In relation to the baseline, VA increased by 0.44 ± 0.24 and 0.29 ± 0.19 logarithm of the minimum angle of resolution units in the IVCD and CT groups, respectively (P < 0.001); however, the difference of VA improvement between the groups was not significant. The interaction effect of IgM and treatment group on lesion size reduction was significant (P = 0.002); this indicated that IgM-positive cases responded better to CT and IgM-negative cases responded better to IVCD treatment. Vitreous inflammation reduction was insignificant between the groups. Within 2 years, 4 eyes (2 in each group) had 1 episode of recurrence. Adverse drug reactions occurred in 2 patients in the CT group. No major injection-related complication was encountered in the IVCD group. CONCLUSIONS: Intravitreal injection of clindamycin and dexamethasone may be an acceptable alternative to the classic treatment in ocular toxoplasmosis. It may offer the patient more convenience, a safer systemic side effect profile, greater availability, and fewer follow-up visits and hematologic evaluations.

Adjustable hybrid diffractive/refractive achromatic lens.

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.

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.

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.

Tunable-focus flat liquid-crystal diffractive lens.

We demonstrate an innovative variable-focus flat liquid-crystal diffractive lens (LCDL) with 95% diffraction efficiency and millisecond switching times using a +/-2.4 V ac input. This lens is based on the electrical modulation of a 3 mum layer of nematic liquid-crystal sandwiched between a Fresnel zone electrode structure and a reference substrate. Each zone is divided into 12 subzones to digitize the phase profiles and define the phase wrapping points. The focusing power can rapidly be switched by electrically changing the number of subzones and re-establishing the wrapping points. Potential applications include zooms with no moving parts and autofocus lenses for compact imaging devices.

Adjustable adaptive compact fluidic phoropter with no mechanical translation of lenses.

We demonstrate a compact optical phoroptor consisting of adjustable astigmatic and defocus lenses. The lenses are fluidically controlled and allow for an arbitrary refractive error to be corrected without mechanically moving lenses. Shack-Hartmann measurements were used to characterize the optical properties of the individual lenses. The lenses were then assembled into the phoropter and controlled with three separate fluid controls. The phoroptor was verified by correcting the vision of a model eye with an induced refraction error.

Nonmechanical bifocal zoom telescope.

We report on a novel zoom lens with no moving parts in the form of a switchable Galilean telescope. This zoom telescope consists of two flat liquid-crystal diffractive lenses with apertures of 10mm that can each take on the focal lengths of -50 and +100cm, with a spacing of 50cm and, hence, a zoom ratio of 4x. The lenses are driven using a low-voltage ac source with 1.6V and exhibit millisecond switching times. The spectral characteristic of this diffractive zoom system is evaluated for light sources of various bandwidths. Potential applications for this technology include a zoom lens with no moving parts for camera phones and medical imaging devices.

Pilot study of intravitreal injection of diclofenac for treatment of macular edema of various etiologies.

PURPOSE: The purpose of this study was to evaluate the effect of a single dose of intravitreal diclofenac, a potent nonsteroidal antiinflammatory drug, on visual acuity and central macular thickness in patients with macular edema of various etiologies. METHODS: In this prospective noncomparative case series, 10 eyes of 10 patients with clinically significant diabetic macular edema (n = 5), neovascular age-related macular degeneration (n = 2), pseudophakic cystoid macular edema (n = 1), macular edema secondary to old branch retinal vein occlusion (n = 1), and cystoid macular edema secondary to chronic intermediate uveitis (n = 1) received 500 microg/0.1 mL of intravitreal diclofenac. The primary outcome measure was change in visual acuity. RESULTS: After 2 weeks, visual acuity improved in 3 (30%) eyes (P = 0.78), did not change in 3 (30%) eyes, and decreased in 3 (30%) eyes. After 4 weeks, improvement of best-corrected visual acuity occurred in 5 (50%) eyes (P = 0.07), but in 3 eyes (30%), best-corrected visual acuity did not change, and in 1 eye (10%), visual acuity decreased. After 8 weeks, visual acuity improved in 7 (70%) eyes (P = 0.019), got worse in 1 eye (10%), and did not change in 2 eyes (20%). Central macular thickness did not decrease significantly at 8 weeks. On the basis of electroretinography, no significant changes in the amplitude of a-wave or b-wave in relation to baseline were noticed in any eye. CONCLUSION: Up to 8 weeks, intravitreal diclofenac treatment of eyes with macular edema of various etiologies yielded prominent improvement in visual acuity but was not associated with a significant decrease in central macular thickness. No toxic effect of intravitreal diclofenac was observed.

Visual outcomes in five different approaches for treatment of central retinal vein occlusion.

BACKGROUND AND OBJECTIVE: Four treatment methods for central retinal vein occlusion were compared with its natural course. PATIENTS AND METHODS: In this partially prospective, comparative, interventional case series on 63 eyes with central retinal vein occlusion, five approaches were compared: intravitreal triamcinolone injection; radial optic neurotomy; combined radial optic neurotomy and intraocular triamcinolone injection; combined internal limiting membrane peeling, radial optic neurotomy, and intraocular triamcinolone; and observation. RESULTS: Final visual acuity in the intravitreal triamcinolone group was better compared with the observation (P = .025), radial optic neurotomy (P = .037), combined radial optic neurotomy/intraocular triamcinolone injection (P = .401), and combined internal limiting membrane peeling, radial optic neurotomy, and intraocular triamcinolone injection (P = .023) groups. However, after adjustment for baseline visual acuity, the only treatment method with significant visual acuity improvement in relation to the observation group was the combined radial optic neurotomy/intraocular triamcinolone injection (P = .025, .023, and .054 at 1, 3, and 6 months, respectively). CONCLUSION: Among the five different approaches analyzed in this study, combined radial optic neurotomy and intraocular triamcinolone injection may provide a better visual outcome in the management of central retinal vein occlusion.

Diagnostic vitrectomy (25-gauge) in a case with intraocular lymphoma masquerading as bilateral granulomatous panuveitis.

PURPOSE: To report a case of intraocular lymphoma, masquerading as bilateral granulomatous panuveitis, and diagnosed after harvesting vitreous specimen with a 25-gauge vitrectomy instrument. METHODS: A 67-year-old woman presented with bilateral granulomatous uveitis. Visual acuity in both eyes was severely impaired because of severe concurrent cataract and vitreous organization. Sutureless phacoemulsification and posterior chamber intraocular lens implantation combined with 25-gauge diagnostic vitrectomy was performed. RESULTS: Cytopathology and immunocytochemistry of the vitreous disclosed a non-Hodgkin B-cell lymphoma despite unremarkable brain MRI, lumbar puncture, bone marrow aspiration, and whole body scan. Visual acuity improved to 20/120 in both eyes. CONCLUSIONS: Sutureless combined 25-gauge diagnostic vitrectomy, phacoemulsification, and posterior chamber intraocular lens implantation during one-stage surgery was effective in obtaining appropriate vitreous material for cytology in a case of intraocular lymphoma.

Randomized trial of intravitreal bevacizumab alone or combined with triamcinolone versus macular photocoagulation in diabetic macular edema.

PURPOSE: To compare the results of intravitreal bevacizumab (IVB) injection alone or in combination with intravitreal triamcinolone acetonide (IVT) versus macular laser photocoagulation (MPC) as a primary treatment of diabetic macular edema (DME). DESIGN: Randomized 3-arm clinical trial. PARTICIPANTS: A total of 150 eyes of 129 patients with clinically significant DME and no previous treatment. METHODS: The eyes were randomly assigned to 1 of the 3 study arms: the IVB group, patients who received 1.25 mg IVB (50 eyes); the IVB/IVT group, patients who received 1.25 mg of IVB and 2 mg of IVT (50 eyes); and the MPC group, patients who underwent focal or modified grid laser (50 eyes). Retreatment was performed at 12-week intervals whenever indicated. MAIN OUTCOME MEASURES: Change in best-corrected visual acuity (VA) at week 24. RESULTS: VA changes among the groups were statistically significant at 6 (P<0.001) and 24 (P = 0.012) weeks. The significant treatment effect was demonstrated in the IVB group at all follow-up visits and in the IVB/IVT group at 6 and 12 weeks. VA changes +/- standard deviation at 36 weeks were -0.28+/-0.25, -0.04+/-0.33, and +0.01+/-0.27 logarithm of minimum angle of resolution in the IVB, IVB/IVT, and MPC groups, respectively (P = 0.053). Significant central macular thickness (CMT) reduction was observed in all groups only up to 6 weeks; however, CMT changes were not significant among the groups in all visits. Overall, retreatment was required for 27 eyes up to 36 weeks (14 in the IVB group, 10 in the IVB/IVT group, and 3 in the MPC group). In the IVB group, in which a greater VA improvement was observed, only 1 injection was required in 72% of the cases. VA improvement >2 Snellen lines at 36 weeks was detected in 37%, 25%, and 14.8% of patients in the IVB, IVB/IVT, and MPC groups, respectively. CONCLUSIONS: Intravitreal bevacizumab injection in patients with DME yielded a better visual outcome at 24 weeks compared with macular photocoagulation. A change in CMT beyond the 6-week time point that corresponded to the vision change was not detected. No adjunctive effect of IVT was demonstrated. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Combination angiostatic therapies: current status.

One of the most important obstacles to combining pharmaceutical agents to treat ocular diseases is the risk of physiochemical reactions. In intraocular administration, these reactions may produce incompatibility, instability, or both. They may change the nature of drug activity, and they may threaten normal cellular function, resulting in lens opacities, corneal toxicity, retinal cell damage, or other adverse outcomes. Although many medications have demonstrated efficacy or have shown promise when administered intravitreally, including antifungals, nonsteroidal antiinflammatory drugs, anti-tumor necrosis factor-alpha agents, mammalian target of rapamycin inhibitors, metalloproteinase inhibitors, antiviral agents, antineoplastic compounds, and antivascular endothelial growth factor therapies, these have been typically tested as single agents. The potential for these agents to be combined will be largely determined by their physiochemical compatibility.