Experimental and analytical quantification of light scattering from vacuoles in intraocular lenses.

PURPOSE: To develop an advanced test methodology for quantification of scattered light from intraocular lenses (IOLs) and to evaluate the correlation between IOL vacuole characteristics and measured scattered light. SETTING: U.S. Food and Drug Administration, Optical Therapeutics and Medical Nanophotonics Laboratory, Silver Spring, Maryland, USA. DESIGN: Experimental and analytical study. METHODS: Twenty-four IOLs containing vacuoles were evaluated using a digital microscopy approach for identifying and characterizing the vacuoles present. A scanning light scattering profiler (SLSP) was used to evaluate and quantify the amount of scattered light from each IOL and from a 25th control IOL without any vacuoles. A variety of IOLs and vacuoles were also modeled in a Zemax simulation of the SLSP, and the simulated scattered light was modeled. RESULTS: The scattered light as measured with SLSP was well correlated with vacuole characteristics, specifically density and size, as measured under the digital microscope for the 24 vacuole-containing IOLs. Additional correlations were found between vacuole sizes, orientations, and the angle at which light was scattered most severely. These correlations were also present in the Zemax model. CONCLUSIONS: Vacuole optical characteristics can be well correlated with measured scatter, demonstrating an ability to predict scattered light based solely on microscope evaluation. Furthermore, the quantitative amount of scatter predicted with Zemax simulations trended closely with the experimentally measured trends.

Quantitative Multiparameter Evaluation of Vacuoles in Intraocular Lenses Employing a High-Magnification Digital Microscopy Method.

As small imperfections with micrometric sizes, fluid-filled vacuoles, also referred to as glistenings, in intraocular lenses (IOLs) have been known to induce significant unwanted light scattering that in several cases presumably cause complaints and sometimes lead to IOL explantation and replacement. This unwanted scatter is of particular concern for patients viewing bright light in reduced-light conditions such as when driving at night, as the scattered light toward the retina can cause temporary blindness. In this study, we have developed and implemented an accurate test methodology based on a high-magnification digital microscopy approach for quantitative multiparameter evaluation and classification of IOL vacuoles depending on their critical optical characteristics including vacuole size, density, shape, and orientation within the IOL material. Using the multiparameter database developed by evaluating vacuole characteristics, we established a classification grading system that can be used to evaluate vacuole effects on light scattering.

Noncontact method for sensing thickness and refractive index of intraocular lens implants using a self-calibrating dual-confocal laser caliper.

We present a fiber-optic dual-confocal laser caliper method for noncontact high-precision sensing and measuring thickness and refractive index of intraocular lens (IOL) implants. The principle of the method is based on sensing and measuring the confocal intensity response of the laser beam reflection from the opposite object surfaces, which provides the advanced feature of having no limitations on the object shape, thickness, and transparency. Using single-mode optical fibers and a 658-nm laser source, the thickness measurement accuracy was assessed to be as high as 5 µm. In addition, refractive index of a transparent object with thickness smaller than the working distance of the focusing lenses can be measured. The thickness and refractive index of a planoconvex IOL were measured with a high accuracy.

Scanning Light Scattering Profiler (SLPS) Based Methodology to Quantitatively Evaluate Forward and Backward Light Scattering from Intraocular Lenses.

The scanning light scattering profiler (SLSP) methodology has been developed for the full-angle quantitative evaluation of forward and backward light scattering from intraocular lenses (IOLs) using goniophotometer principles. This protocol describes the SLSP platform and how it employs a 360° rotational photodetector sensor that is scanned around an IOL sample while recording the intensity and location of scattered light as it passes through the IOL medium. The SLSP platform can be used to predict, non-clinically, the propensity for current and novel IOL designs and materials to induce light scatter. Non-clinical evaluation of light scattering properties of IOLs can significantly reduce the number of patient complaints related to unwanted glare, glistening, optical defects, poor image quality, and other phenomena associated with the unintended light scattering. Future studies should be conducted to correlate SLSP data with clinical results to help identify which measured light scatter is most problematic for patients that have undergone cataract surgery subsequent to IOL implantation.

Confocal laser method for quantitative evaluation of critical optical properties of toric intraocular lenses.

PURPOSE: To present a proof-of-concept study on the development and implementation of an innovative confocal laser method platform for precise quantitative evaluation of critical optical properties unique to toric intraocular lenses (IOLs). SETTING: U.S. Food and Drug Administration, Optical Therapeutics and Medical Nanophotonics Laboratory, Silver Spring, Maryland, USA. DESIGN: Experimental study. METHODS: The optical properties of hydrophobic toric IOLs were evaluated with a confocal laser method that was modified to isolate the 2 planes of focus that are observed with toric IOLs. RESULTS: The results show the confocal laser method has the potential to measure the orthogonally separated optical powers and then calculate them to the commonly referenced spherical equivalent and cylinder powers of toric IOLs with high accuracy (≤1 µm of focal length measurement). Furthermore, the proposed confocal laser method design includes a new component for precise differentiation of the 2 focal planes and isolation of the 2 focal points, and thus for accurate measurement of the anterior cylinder axis of toric IOLs. CONCLUSION: The modifications to the confocal laser method platform enabled the quantitative evaluation of optical properties attributed to toric IOLs. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.

A novel full-angle scanning light scattering profiler to quantitatively evaluate forward and backward light scattering from intraocular lenses.

Glare, glistenings, optical defects, dysphotopsia, and poor image quality are a few of the known deficiencies of intraocular lenses (IOLs). All of these optical phenomena are related to light scatter. However, the specific direction that light scatters makes a critical difference between debilitating glare and a slightly noticeable decrease in image quality. Consequently, quantifying the magnitude and direction of scattered light is essential to appropriately evaluate the safety and efficacy of IOLs. In this study, we introduce a full-angle scanning light scattering profiler (SLSP) as a novel approach capable of quantitatively evaluating the light scattering from IOLs with a nearly 360° view. The SLSP method can simulate in situ conditions by controlling the parameters of the light source including angle of incidence. This testing strategy will provide a more effective nonclinical approach for the evaluation of IOL light scatter.

Assessing the effect of laser beam width on quantitative evaluation of optical properties of intraocular lens implants.

The design and manufacture of intraocular lenses (IOLs) depend upon the identification and quantitative preclinical evaluation of key optical properties and environmental parameters. The confocal laser method (CLM) is a new technique for measuring IOL optical properties, such as dioptric power, optical quality, refractive index, and geometrical parameters. In comparison to competing systems, the CLM utilizes a fiber-optic confocal laser design that significantly improves the resolution, accuracy, and repeatability of optical measurements. Here, we investigate the impact of changing the beam diameter on the CLM platform for the evaluation of IOL dioptric powers. Due to the Gaussian intensity profile of the CLM laser beam, the changes in focal length and dioptric power associated with changes in beam diameter are well within the tolerances specified in the ISO IOL standard. These results demonstrate some of the advanced potentials of the CLM toward more effectively and quantitatively evaluating IOL optical properties.

Impact of environmental temperature on optical power properties of intraocular lenses.

Optical power properties of lenses and materials in general can be influenced by thermal changes of the material and surrounding medium. In the case of an intraocular lens (IOL) implant, the spherical power (SP), cylinder power, (CP), astigmatism, and spherical aberration are the critical fundamental properties that can significantly impact its efficacy. Directly evaluating how changes in temperature can affect these optical properties may show the importance of considering temperature when evaluating IOL optical characteristics. In this paper, we present a quantitative study on evaluating the impact of environmental temperature changes on IOL fundamental optical properties by testing IOL samples with different materials (e.g., hydrophobic and hydrophilic) and designs (e.g., monofocal and toric) to better encompass types of IOLs in conventional use today. The results from this study demonstrate that significant changes are observed as temperatures are changed from room temperature (20°C) to slightly above body temperature (40°C). Findings indicate that evaluating optical properties at arbitrary temperatures could significantly affect the characterization of IOLs that are already near the tolerance thresholds.

Evaluation of intraocular reactivity to metallic and ethylene oxide contaminants of medical devices in a rabbit model.

OBJECTIVE: To evaluate the intraocular reactivity to metallic and ethylene oxide (EO) contaminants of ophthalmic devices in rabbits. DESIGN: Two experimental animal studies. PARTICIPANTS: Thirty-five New Zealand white rabbits. METHODS: A metallic exposure study and an EO exposure study were performed. In the first study, both eyes of 25 rabbits were equally allocated to intracameral injections of alumina 0.2 µg, alumina 20 µg, copper sulfate 0.4 µg, copper sulfate 20 µg, or an aqueous control. In the second study, 10 rabbits were allocated (5 per group) to receive intracamerally an ophthalmic viscosurgical device (OVD) exposed to EO or not exposed to EO (control). All eyes were examined by slit lamp at baseline and 3, 6, 9, 24, 48, and 72 hours after exposure, with dilated indirect ophthalmoscopy being performed at 24 and 72 hours. Tonometry was performed only in the first study. MAIN OUTCOME MEASURES: Grade of corneal clouding, anterior chamber (AC) flare, AC cells, AC fibrin, iridal hyperemia, cell and fibrin on the lens surface, vitreous haze and cells, lens opacities, intraocular pressure, and onset time. RESULTS: For metallic compounds at the study's low doses, mean inflammatory grades were 0.2 or less above the control for all responses at all time points. For the high-dose alumina, mean inflammatory grades peaked at 6 to 9 hours at 0.5 to 0.7 above the control responses for conjunctival congestion, iris hyperemia, AC cells, flare, and fibrin and declined over the remaining time points. For the high-dose copper sulfate, mean inflammatory grades peaked between 3 and 24 hours at 1.2 to 1.8 above the control responses for conjunctival congestion, iris hyperemia, AC cells, flare, fibrin, and corneal clouding, then subsequently declined. The intraocular pressure changes appeared significant for only high-dose copper sulfate, with mean declines of 4.3 to 7.5 mmHg at 6 to 72 hours. No clinically meaningful differences in ocular inflammation were observed between the OVD exposed to EO and the OVD not exposed to EO. CONCLUSIONS: Alumina and copper sulfate did not cause clinically meaningful ocular inflammation at the low study levels (levels expected with ophthalmic devices). Ethylene oxide exposure of an OVD was not associated with inflammation.

An investigation of enzymatic detergents as a potential cause of toxic anterior segment syndrome.

OBJECTIVE: To investigate whether enzymatic detergents used in cleaning ophthalmic surgical instruments can cause toxic anterior segment syndrome (TASS)-like responses in a rabbit model. DESIGN: Randomized, investigator-masked, controlled experimental animal study. PARTICIPANTS: Thirty-five New Zealand white rabbits. METHODS: The rabbit eyes were randomized into 7 treatment groups to receive intracameral injection of 1 of 3 different doses of Medline Dual Detergent or Enzol Detergent, or sterile limulus amoebocyte lysate reagent water as a control. The eyes were evaluated for anterior segment inflammation at baseline and at 1, 3, 6, 24, 48, and 72 hours after treatment by slit-lamp biomicroscopy. MAIN OUTCOME MEASURES: Anterior chamber (AC) inflammation, including cells, flare, fibrin, and iris injection; time course of inflammation; and residual detergent levels in luminated instruments. RESULTS: Moderate to marked injection of the iris vessels was seen as early as 1 hour after treatment with the enzymatic detergents in 41 of 60 eyes, with the response being more severe in the Enzol Detergent-exposed eyes. Severe iris hemorrhages were accompanied by blood in the AC in 13 eyes, which usually persisted through 72 hours, with an associated increase in AC cell and flare. Corneal haze was present in 52 of 56 eyes 1 hour after treatment, but was mild and resolved within 24 hours in all but the Enzol 4.5%-exposed eyes. Median AC cell and flare peaked at 6 hours and resolved by 48 hours. CONCLUSIONS: Enzymatic detergents caused a severe but unusual response from the iris when injected intracamerally into rabbit eyes. This response has not been reported in humans with TASS. The time course of inflammation was faster (peak at 6 hours) and resolved more quickly (within 48 hours) than TASS. Simulated cleaning and extraction studies indicate that the level of residual detergent to which a patient could be exposed is significantly less than the lowest dose used in this study. Because that low dose caused no significant observations other than injection of the iris vessels, these results do not support residual enzymatic detergents on surgical instruments as a cause for TASS.

The Food and Drug Administration's Proactive toxic anterior segment syndrome Program.

Toxic anterior segment syndrome (TASS) is a rare inflammatory condition usually observed within the first 48 hours after uncomplicated anterior segment surgery. Over the decades since its initial description, a number of TASS outbreaks have been reported. For a few of these outbreaks, the inciting factors were identified, but for the majority, the precipitating factors were often postulated but not confirmed. In light of the limitations identified in these outbreak investigations, the Food and Drug Administration's (FDA's) Center for Devices and Radiological Health staff has embarked on a number of activities aimed at mitigating medical device-related TASS outbreaks. Under the FDA-designed Proactive TASS Program (PTP), FDA scientists have conducted animal studies to better explore the inflammatory potential of suspected ophthalmic device contaminants implicated in prior cases of TASS. For contaminants displaying a TASS-like reaction in these animal models, the FDA scientists have developed analytic test methods to measure the level of those contaminants in or on ophthalmic devices. Moreover, FDA researchers have developed methods to better capture the clinical information necessary to assist investigations of potential future outbreaks. Last, the FDA has partnered with the Centers for Disease Control and Prevention to facilitate a potential TASS investigation, including expediting the analysis of potentially contaminated medical devices. The PTP is an example of the FDA proactively developing test methods and disease surveillance methods geared toward protecting the public's health.

Rabbit intraocular reactivity to endotoxin measured by slit-lamp biomicroscopy and laser flare photometry.

OBJECTIVE: To evaluate the ocular reactivity of the rabbit to an intracameral injection of a dispersive ophthalmic viscosurgical device (OVD) containing various levels of bacterial endotoxin using slit-lamp biomicroscopy and laser flare photometry. DESIGN: Experimental, randomized, masked animal study. PARTICIPANTS: Thirty Dutch-Belted rabbits. METHODS: The rabbits were randomized into 6 groups to receive 0.05 ml of a hydroxypropyl methylcellulose-based dispersive OVD to which had been added one of 5 different doses of bacterial endotoxin ranging from 0.02 to 1.4 endotoxin units (EUs) or a vehicle control to both eyes. The eyes were evaluated for anterior segment inflammation at baseline and 3, 6, 9, 24, 48, and 72 hours after injection using slit-lamp biomicroscopy and laser flare photometry. MAIN OUTCOME MEASURES: Corneal clarity and anterior chamber (AC) inflammation. RESULTS: All the corneas remained clear throughout the study. Anterior chamber cells were seen at 6, 9, and 24 hours in 60% to 100% of the eyes intracamerally injected with endotoxin-containing OVD, and the response declined rapidly after 24 hours. A dose-response effect was seen between the concentration of endotoxin and the AC cell response. The aqueous flare response in eyes injected with the 2 highest doses of endotoxin was significantly greater (P<0.05) than that of controls. The amounts of fibrin observed in the AC were random, with no apparent dose-response effect seen. The flare values as obtained by laser flare photometry were consistent with the slit-lamp biomicroscopy flare findings up to grade 3+. However, the increase in laser flare value seemed to level off in eyes with more than 3+ flare. Neither measure of flare correlated with endotoxin level. CONCLUSIONS: Among the parameters evaluated in this study, the AC cell response, evaluated by slit-lamp biomicroscopy and graded using a standard grading system, was found to be the most reliable indicator of the amount of endotoxin in the dispersive OVD. The use of laser flare photometry alone does not seem to be useful in detecting an ocular response to endotoxin contamination in OVDs.

Evaluation of intraocular reactivity to organic contaminants of ophthalmic devices in a rabbit model.

OBJECTIVE: To evaluate the intraocular reactivity to organic contaminants of ophthalmic devices in the rabbit. DESIGN: Experimental animal study. PARTICIPANTS: Fifty New Zealand white rabbits. METHODS: The rabbits were allocated to 10 groups of 5 each to receive 2 different doses of human albumin and nonhuman nucleic acids and their respective vehicle controls, a denatured cohesive ophthalmic viscosurgical device (OVD) and a denatured dispersive OVD and their respective nondenatured controls. All 10 eyes in each treatment group received bilateral intracameral injection of the test materials. All the eyes in the study were examined by slit-lamp biomicroscopy at baseline and 6, 9, 24, 48, and 72 hours. Pachymetry was also performed on eyes exposed to albumin, protein vehicle control, and the OVDs at these time points. MAIN OUTCOME MEASURES: Corneal thickness, grade of corneal clouding, anterior chamber (AC), cells, flare and fibrin, iridal hyperemia, cell and fibrin on lens surface, and onset time. RESULTS: There were no inflammatory signs in any eyes exposed to human albumin. Anterior chamber cells (1+ to 3+) and flare and fibrin (1+ to 2+), along with cells and fibrin on the lens surface, were seen in the eyes exposed to the nucleic acid samples, and they resolved in 24 hours. Mild (mostly 1+) conjunctival congestion, cells, flare, and fibrin were seen in a few eyes exposed to the 2 denatured OVDs and their controls, with the response durations being shorter in the denatured OVD eyes (24 hours) than in the nondenatured OVD eyes (48 hours). Anterior chamber inflammation was generally observed in fewer denatured OVD eyes than in nondenatured OVD eyes, particularly the dispersive OVD eyes. CONCLUSIONS: Intracameral injection of human albumin protein did not cause ocular inflammation. Nucleic acid intracamerally injected into rabbit eyes caused acute inflammation that quickly resolved. Cohesive and dispersive OVD denatured by drying and steam sterilization alone did not cause ocular inflammation.