Placebo Eyes Research Articles

Does the Visual Field Improve After Initiation of Intraocular Pressure Lowering in the United Kingdom Glaucoma Treatment Study?

PurposeEvidence to support the hypothesis that visual field (VF) status can improve after initiation of intraocular pressure (IOP) reducing treatment is controversial. We take advantage of participant eligibility data from the United Kingdom Glaucoma Treatment Study (UKGTS) to test this hypothesis in newly diagnosed glaucomatous patients randomised to IOP lowering therapy or placebo. DesignMulticentre, randomised, triple-masked, placebo-controlled trial. ParticipantsNewly diagnosed open-angle glaucoma patients in the UKGTS with eligibility and baseline data (n = 202 and n = 205 participants from the treatment and placebo groups, respectively). MethodsUKGTS eligibility data, including two reliable VFs (Humphrey 24-2 SITA Standard) and IOP measurements were compared to UKGTS trial baseline data acquired after allocation to treatment (topical prostaglandin analog) or placebo eye drops. Mean change in VF mean deviation (MD) and proportion of eyes that improved MD by more than different thresholds were compared across this interval in the treatment and placebo groups. Secondary analyses included stratifying the groups by level of IOP, level of VF loss and age along with pointwise analyses including change in subsets of VF locations. Main outcome measureMean change in VF MD. ResultsMean (standard deviation [SD]) time between eligibility/baseline visits and reduction in IOP was 12 (3) weeks and 4.8 (4.2) and 1.0 (3.6) mmHg for the treated and placebo eyes, respectively. Mean (SD) change in MD was almost the same for the treated (-0.03 (1.45) dB) and placebo groups (+0.08 (1.72) dB) (P=0.47). Proportion of participants with an MD improvement of 1 dB or more were similar for both groups (P=0.25). No association was found between MD improvement and magnitude of IOP lowering. Stratifying data by IOP, level of VF loss and age did not reveal any differences between the treated and placebo groups and neither did any of the pointwise VF analyses. ConclusionInitial short-term VF changes in the treatment and placebo arms of UKGTS were the same. In these newly diagnosed patients (non-advanced glaucoma) we found no evidence to support the hypothesis that VF status improves after initial lowering of IOP by medical therapy.

Efficacy of perioperative 2% dorzolamide ophthalmic solution for reduction of postoperative ocular hypertension in dogs following routine phacoemulsification surgery: A prospective clinical trial.

To evaluate the efficacy of 2% dorzolamide ophthalmic solution for reduction of postoperative ocular hypertension (POH) following routine phacoemulsification surgery in dogs. Thirty one dogs (53 eyes) with naturally occurring cataracts undergoing routine phacoemulsification surgery. A prospective, double-masked, randomized, placebo-controlled study design was utilized. Dogs received 2% dorzolamide ophthalmic solution or saline 1 h prior to surgery then three times daily for 21 days postoperatively in the operated eye(s). Intraocular pressure (IOP) was recorded 1 h prior to surgery and 3 h, 7 h, 22 h, 1 week and 3 weeks postoperatively. Statistical analyses were performed using chi-squared and Mann-Whitney U test with a significance level of p < .05. Postoperative ocular hypertension (IOP ≥25 mmHg, <24 h after surgery) occurred in 28/53 (52.8%) eyes. There was significant reduction in the incidence of POH for eyes receiving dorzolamide (10/26 (38.4%) eyes) versus eyes receiving placebo (18/27 (66.7%) eyes) (p = .0384). Animals were followed for a median of 163 days after surgery. Thirty-seven (37/53 (69.8%)) eyes were visual at final examination and 3/53 (5.7%) globes were enucleated postoperatively. At last follow-up, there was no difference in visual status (p = .9280), need for topical IOP lowering medication (p = .8319) or incidence of glaucoma (p = .5880) based on treatment group. Perioperative administration of topical 2% dorzolamide reduced the incidence of POH after phacoemulsification in the dogs studied. However, this was not associated with differences in visual outcome, incidence of glaucoma or need for IOP-lowering medications.

The phase 3 REFLECT trial: Efficacy and safety of bilateral gene therapy for Leber hereditary optic neuropathy (LHON)

AbstractPurpose: To evaluate the efficacy and safety of a bilateral injection of lenadogene nolparvovec in patients with Leber Hereditary Optic Neuropathy (LHON) carrying the m.11778G &gt; A mutation.Methods: REFLECT is a randomized, placebo‐controlled, phase 3 study that included 98 patients with vision loss ≤1 year at enrolment. Patients received a single intravitreal injection of lenadogene nolparvovec (9E10 viral genomes per eye) in their first‐affected eye. The second‐affected eye was randomized to a second injection of gene therapy or placebo.Results: A total of 48 patients were treated bilaterally and 50 unilaterally. At 1.5 years, the change from baseline in best‐corrected visual acuity (BCVA) of the second‐affected eyes was not statistically different between the two arms (primary endpoint). Two years after injection, a statistically significant improvement in BCVA was reported from baseline in treated eyes. Mean BCVA showed an absolute difference between the arms of +6 ETDRS letters in favour of bilaterally treated patients. The improvement from nadir was +20 and +17 letters for the first‐ and second‐affected eyes treated bilaterally, and +19 and +14 letters for first‐ and second‐affected eyes treated unilaterally (all p &lt; 0.0001). Clinically meaningful improvement from nadir ≥ +15 letters was found in the majority of bilaterally and unilaterally treated patients (73% and 66%, respectively). The main ocular adverse event related to gene therapy was intraocular inflammation, which was mostly mild and responsive to conventional treatment. Overall, the safety profile was favourable and comparable in patients treated unilaterally and bilaterally.Conclusions: The 2‐year data confirm the results observed 1.5 years after treatment: bilaterally treated patients have better improvement of BCVA than unilaterally treated patients with a favourable safety profile. Placebo eyes showed a contralateral therapeutic effect as previously observed in the RESCUE and REVERSE trials.

Effect of Topically Applied 0.5% Apraclonidine Versus 0.5% Timolol Maleate on Intraocular Pressure of Healthy Horses

This study aims to assess the effect of topical 0.5% apraclonidine on Intraocular pressure (IOP) in horses and compare the effects of timolol maleate 0.5% with 0.5% apraclonidine in the equine eye. Twenty healthy female thoroughbred horses were used. Horses were divided into two groups. Ten horses received single dose of 0.2 mL of 0.5% apraclonidine in one randomly selected eye and the contralateral eye received single dose of 0.2 mL of artificial tears. In the second group, 10 horses received single dose of 0.2 mL of 0.5% timolol maleate in one eye and the opposite eye received single dose of placebo (0.2 mL of artificial tears). Intraocular pressure was measured using rebound tonometer at the baseline and 30, 60, 120, 240, 360 minutes, and 24 hours after topical ophthalmic drops instillation. Any ocular side effects were recorded at each time point. Mean (SD) baseline IOPs of the treated and placebo eyes were 26.2(3.1) and 23.5(3.4) in apraclonidine group, and 25.7(2.6) and 23.2(3.3) in timolol group. In the apraclonidine group, significant reduction in the mean IOP started after 60 minutes (P= .005) and was still present after 24 hours (P < .001). In timolol group, IOP was reduced in the treated eyes, but this reduction was only significant in the treated eyes at T24h (P= .03). The highest reduction in IOP in timolol group was observed at T360 (21.0(2.2); 14.7%). Mean IOP was decreased prominently by apraclonidine compared to timolol in treated eyes. In conclusion, single dose of topical 0.5% apraclonidine reduced IOP significantly among normal horses in the present study. Further investigations are necessary for evaluating efficacy and safety of apraclonidine in horses.

A Randomized Trial of Photobiomodulation Therapy for Center-Involved Diabetic Macular Edema with Good Visual Acuity (Protocol AE)

To determine if treatment with a photobiomodulation (PBM) device results in greater improvement in central subfield thickness (CST) than placebo in eyes with center-involved diabetic macular edema (CI-DME) and good vision. Phase 2 randomized clinical trial. Participants had CI-DME and visual acuity (VA) 20/25 or better in the study eye and were recruited from 23 clinical sites in the United States. One eye of each participant was randomly assigned 1:1 to a 670-nm light-emitting PBM eye patch or an identical device emitting broad-spectrum white light at low power. Treatment was applied for 90 seconds twice daily for 4 months. Change in CST on spectral-domain OCT at 4 months. From April 2019 to February 2020, 135 adults were randomly assigned to either PBM (n= 69) or placebo (n= 66); median age was 62 years, 37% were women, and 82% were White. The median device compliance was 92% with PBM and 95% with placebo. OCT CST increased from baseline to 4 months by a mean (SD) of 13 (53) μm in PBM eyes and 15 (57) μm in placebo eyes, with the mean difference (95% confidence interval [CI]) being-2 (-20 to 16) μm (P= 0.84). CI-DME, based on DRCR Retina Network sex- and machine-based thresholds, was present in 61 (90%) PBM eyes and 57 (86%) placebo eyes at 4 months (adjusted odds ratio [95% CI]= 1.30 (0.44-3.83); P= 0.63). VA decreased by a mean (SD) of-0.2 (5.5) letters and-0.6 (4.6) letters in the PBM and placebo groups, respectively (difference [95% CI]= 0.4 (-1.3 to 2.0) letters; P= 0.64). There were 8 adverse events possibly related to the PBM device and 2 adverse events possibly related to the placebo device. None were serious. PBM as given in this study, although safe and well-tolerated, was not found to be effective for the treatment of CI-DME in eyes with good vision.

Safety and efficacy of unilateral topical application of rocuronium bromide in healthy scops owls (Otus scops).

To evaluate the safety and efficacy of unilateral topical application of rocuronium bromide in scops owls. Ten healthy adult scops owls. Birds weighting between 82-111g were enrolled. Complete physical and ophthalmic examinations were performed. Each animal received a single dose of 0.15mg of rocuronium bromide (30µL) in a randomly selected eye. Static pupillometric evaluations were performed before and after drug instillation at 0, 30, 60, 90, and 120minutes, in a room with fixed light intensity. Physical and ophthalmic examinations were carried out to evaluate possible adverse effects. Median pupil (95% CI) size at t0 was 7.10mm (5.51-7.41) for placebo eyes and 7.22mm (6.93-7.48) for treated eyes, showing no statistical differences (P>.05). When compared to the placebo eye, significant mydriasis was achieved at t30 [8.18mm (7.22-9.00)] (P=.014) and lasting until t90 [7.35mm (6.20-9.52)] (P=.004). Maximal mydriasis was obtained at t60 [8.63mm (7.72-9.81)] (P=.001). During this period, the treated eye no longer responded to direct light stimulation. Complete mydriasis was observed in 5/10 birds (mean weight 97.4g). Pupil size at t90 and t120 did not differ from baseline (P>.05) in treated eyes. No adverse effects were seen during the study period. Single-dose topical rocuronium bromide (0.15mg) is a safe and effective medium duration mydriatic agent in scops owls. Further studies are needed to evaluate bilateral topical application and standardize the mydriatic protocol.

Intravitreal Triamcinolone Acetonide Injection in a Rodent Model of Anterior Ischemic Optic Neuropathy.

The management of nonarteritic anterior ischemic optic neuropathy centers around prevention of second eye involvement, without a uniformly accepted therapy for the involved eye. Several researchers have assessed the benefit of steroids with conflicting results. This experimental study was designed to evaluate the efficacy of a single intravitreal triamcinolone acetonide injection (IVTA) in preserving retinal ganglion cells (RGCs) in a rodent model of anterior ischemic optic neuropathy (rAION). The rAION was induced in female Wistar rats. Animals were randomized into 3 groups: 1) untreated, 2) treated with 56 μg IVTA, and 3) intravitreal saline (placebo). Procedures were performed in the left eye, with the right eye serving as control. After 30 days, animals were sacrificed and eyes were assessed histologically for RGC number. The average number of RGC was significantly lower in rAION subgroups when compared with the control group (P < 0.001). No significant difference was seen between rAION eyes treated with IVTA, placebo, and untreated eyes (P > 0.05%). In this rodent model for AION, no therapeutic benefit of intravitreal steroid injection was identified.

Fluorometholone 0.1% as Ancillary Therapy for Trachomatous Trichiasis Surgery: Randomized Clinical Trial

To assess the hypothesis that fluorometholone 0.1% eye drops are safe and effective as adjunctive therapy for trachomatous trichiasis (TT) surgery; determining the most promising dose. Randomized, placebo-controlled, double-masked parallel dose-ranging clinical trial. Patients undergoing upper lid TT surgery at a rural Ethiopian hospital were randomized to fluorometholone 0.1% twice daily for 4weeks, 4 times daily for 4weeks, 4 times daily for 8weeks, or matching frequency placebo in a 3:1:3:1:3:1 ratio for 1 eye. Randomization was stratified by TT severity (1-4 vs ≥5 lashes touching the globe). Safety outcomes (intraocular pressure [IOP] elevation, cataract, and other dose-limiting toxicities) and postoperative TT incidence were assessed over 1 year. Subjects randomized were 39:13:39:13:38:13 in the respective groups, and 1 subject in the 8-weeks fluorometholone group was withdrawn. Of 154 subjects, 148 (96.1%) completed 1 year's follow-up. Among 76 eyes receiving fluorometholone 4 times daily, 1 developed IOP elevation ≥ 30mm Hg (to 37mm Hg) and 1 had an allergic reaction attributed to the study drug; each resolved upon drug cessation without sequelae. No cataract or other dose-limiting toxicity events occurred. Postoperative TT within 1 year occurred in 29.3% of placebo eyes vs 17.7%, 19.6%, and 23.2% among the respective fluorometholone groups (P= .29 comparing placebo vs all active treatments combined). The results suggest fluorometholone 0.1% is likely to be safe and efficacious to reduce postoperative TT following TT surgery, and 1 drop twice daily for 4weeks is the most promising dose. Confirmation in a full-scale clinical trial is needed before programmatic implementation.

The Effects of Netarsudil Ophthalmic Solution on Aqueous Humor Dynamics in a Randomized Study in Humans.

Purpose: Netarsudil, an inhibitor of Rho kinase and a norepinephrine transporter, has been shown to lower elevated intraocular pressure (IOP) in controlled studies of patients with open-angle glaucoma and ocular hypertension, and in healthy volunteers. The mechanism of this ocular hypotensive effect in humans is unknown.Methods: The objective of this study was to evaluate the effect of netarsudil 0.02% on aqueous humor dynamics (AHD) parameters. In this double-masked, vehicle-controlled, paired-eye comparison study, 11 healthy volunteers received topical netarsudil ophthalmic solution 0.02% or its vehicle once daily for 7 days (morning dosing). The primary endpoints were the change in AHD parameters, compared between active and vehicle-treated eyes.Results: In netarsudil-treated eyes, diurnal outflow facility increased from 0.27 ± 0.10 μL/min/mmHg to 0.33 ± 0.11 μL/min/mmHg (+22%; P = 0.02) after 7 days of treatment. In placebo-treated eyes, diurnal outflow facility did not significantly change (P = 0.94). The difference between netarsudil and placebo eyes in diurnal change of outflow facility was 0.08 μL/min/mmHg (P < 0.001). Diurnal episcleral venous pressure (EVP) in netarsudil-treated eyes decreased from 7.9 ± 1.2 mmHg to 7.2 ± 1.8 (-10%; P = 0.01). Diurnal EVP was not significantly different between netarsudil- and placebo-treated eyes. There was a trend toward decreasing aqueous humor flow rate (-15%; P = 0.08). No treatment changes were seen in uveoscleral outflow rate.Conclusions: Once-daily dosing of netarsudil ophthalmic solution 0.02% lowered IOP through increasing trabecular outflow facility and reducing EVP. This suggests a combination of mechanisms that affect both the proximal and distal outflow pathways.

Effect of Coherin™ on intraocular pressure, pupil size and heart rate in the glaucomatous Beagle: a pilot study

To evaluate effects of Coherin™ on intraocular pressure (IOP), pupil size (PS), and heart rate (HR) in glaucomatous Beagles in single-dose studies in a pilot study. Intraocular pressure, PS, and HR were measured in eight glaucomatous Beagles. One randomly chosen eye received single 50 μL doses of differing concentrations of Coherin™ (treated eye) or vehicle (placebo-treated eye), and the fellow eye served as the untreated control. After the first measurements, a single dose of either Coherin™ or sterile water vehicle was instilled in the drug and placebo eyes, respectively. The mean ± SEM diurnal changes in IOP after 0.005%, 0.01%, 0.2%, 0.284%, 1%, 2%, and 4% topical Coherin™ once daily were 7.6 ± 3.2 mmHg, 15.5 ± 5.3 mmHg, 11.2 ± 4.4 mmHg, 11.8 ± 4.4 mmHg, 19.1 ± 3.8 mmHg, 5.0 ± 1.8 mmHg, and 8.8 ± 2.8 mmHg, respectively. The declines in IOP were significantly different (P < 0.05) from the untreated control eyes with the 0.2% and 0.284% Coherin™-treated eyes and suggestive for 1% Coherin™ concentrations. No signs of irritation, significant PS, and HR changes were detected in the Coherin™-treated eyes. Of seven different concentrations, 2% and 0.248% Coherin™ produced significant declines in IOP in the glaucomatous beagle in single-dose studies when compared to both untreated control and placebo-treated eyes. One percent Coherin™ solution produced significant IOP decreases compared with the placebo-treated eye but not the untreated control eyes. No local ocular irritation, PS and HR changes were observed in Coherin™-treated eyes. This pilot study suggests that topical Coherin™ has potential as an ocular hypotensive agent.

Effects of concomitant administration of latanoprost and pilocarpine on the intraocular pressure of experimentally glaucomatous rabbits

Summary The purpose of this study was to evaluate the effects of a combination of latanoprost and pilocarpine on the intraocular pressure in experimentally glaucomatous rabbits. Ocular hypertension was induced in 11 conscious rabbits by the oral administration of tap water (70 mL/kg) via an orogastric tube. The study was conducted in three therapeutic groups to test the effects of latanoprost (group L), pilocarpine (group P) and a combination of the two drugs (group LP). After evaluating the first drug, a washout period of 1 week was allowed before the second drug was evaluated. The left eye of rabbits in group L received one drop of normal saline and one drop of 0.005% latanoprost, in group P one drop of normal saline and one drop of 2% pilocarpine and in group LP, one drop of 0.005% latanoprost and one drop of 2% pilocarpine. The right eyes of all rabbits received two drops of normal saline (as control eyes). The intraocular pressure (IOP) and pupil diameter (PD) were measured before and at 0, 15, 30, 45, 60, 75, 90, 105 and 120 min post-water loading. The results showed that eyes, which received pilocarpine had a significantly lower increase in IOP at 15, 30, 45 and 60 min after drug administration compared to placebo eyes, whereas groups L and LP did not prevent an IOP increase. The PD decreased in groups P and LP throughout the study, whereas it did not change in group L. It was concluded that the topical administration of latanoprost alone or in combination with pilocarpine appeared to have no effect on IOP in acute ocular hypertensive rabbits.

Efficacy of Pulsed Electromagnetic Energy in Postoperative Recovery from Blepharoplasty

A novel medical device that has been approved by the Food and Drug Administration is available for treatment of postsurgical edema. The device emits a low-level, pulsed electromagnetic energy field, which modulates resting cell membrane potential, allowing a return to physiologic resting membrane potential. To investigate the benefits of electromagnetic energy in eyelid wound healing. Fifty-seven individuals participated in this randomized, double-blinded study. All patients underwent upper blepharoplasty. At the postoperative visit, patients rated pain, edema, and ecchymosis, and the physician rated edema, ecchymosis, and erythema. There was no difference (p=.76) in patient pain rating when comparing placebo (1.6) with the patch (1.3). Patients reported 6% less edema (p=.11) and 10% less ecchymosis (p=.17) with the active patch eye than in control eye. The physician-graded edema, ecchymosis, and erythema had a mean Likert-type scale difference between placebo and active eyes of -0.3 (p=.12), -0.3 (p=.17), and -0.2 (p=.004) respectively. The use of pulsed electromagnetic energy did not have an effect on postoperative pain, edema, or ecchymosis as rated by patients and physicians. There was a statistically significant reduction in physician-graded erythema for active patch eyes versus placebo.

Topical Ketorolac 0.5% for Ocular Pain Relief During Scatter Laser Photocoagulation with 532 nm Green Laser

The aim of this study was to evaluate the analgesic effect of topical ketorolac tromethamine 0.5% during scatter laser photocoagulation procedure in proliferative diabetic retinopathy patients. 60 eyes of 30 consecutive proliferative diabetic retinopathy patients were included to this prospective, randomized, double-masked, controlled study. One (1) h before laser treatment session, ketorolac tromethamine 0.5% was instilled to 1 eye and artificial tear drop to the fellow eye. Just after treatment, the patients were asked for the severity of pain in both eyes. Visual analog scale was used to assess the level of pain. Mean pain level for placebo-instilled eyes was 4.88+/-2.56 and ketorolac instilled eyes were 4.45+/-2.25. There was no significant difference for pain levels between placebo and ketorolac-instilled eyes (P=0.29). Topical ketorolac tromethamine usage is no more effective than artificial tears for pain relief during posterior segment laser procedures in proliferative diabetic retinopathy patients.

Clinical outcomes and mechanism of action for rheopheresis treatment of age-related macular degeneration (AMD)

The primary goals are to provide a comprehensive explanation of the potential role of therapeutic apheresis in the treatment of Age-Related Macular Degeneration (AMD). Initial clinical results with this technique and a summary of current literature that addresses the mechanism of action for the Rheopheresis approach are presented. Rheopheresis has been found to be a safe and effective application of double filtration plasmapheresis (DFPP) for extracorporeal hemorheotherapy. In this report, it is proposed that Rheopheresis results in an immediate decrease in the proportion of high molecular weight proteins that could combine with the TIMP-3 fibulin complex allowing for the barely functioning retinal pigment epithelial (RPE) cells to function better and diminish the release of vascular endothelial growth factor (VEGF). Interim results from the randomized, double-masked MIRA-1 clinical trial include (1) improved vision restoration; 28.0% of Treated Primary Eyes increased by > or = 2 lines of best corrected visual acuity (BCVA) compared to 18.2% of Placebo Eyes; (2) a decline in progressive vision loss; 0.0% of treated eyes progressing to worse than 20/200 vision over the 12-month study compared to 18.2% of Placebo Eyes; (3) 57.9% of Treatment Eyes obtained improvement in their BCVA to 20/40 or better (driver's license qualification), compared to only 14.3% of Placebo Eyes 12-month post-treatment. Rheopheresis treatment shows strong promise as a viable clinical option for patients suffering from the dry form of AMD in terms of minimizing vision loss, vision restoration, and overall quality of life factors. Expanded clinical outcomes from the ongoing MIRA-1 clinical study will be valuable in the assessment of this new clinical tool for ophthalmic applications.

Effect of Topical Levobunolol on Retinal, Optic Nerve Head, and Choroidal Circulation in Normal Volunteers

Purpose: Using three different techniques of ocular blood flow measurement, we evaluated the effects of topical levobunolol on retinal, optic nerve head, and choroidal circulation. Methods: Twenty normal volunteers received one drop of levobunolol in one eye and one drop of placebo in the fellow eye. Retinal venous blood flow was measured using multiple scattering laser velocimetry. Retinal capillary blood flow and optic nerve head blood flow were measured by Heidelberg Retina Flowmeter ®. Pulsatile ocular blood flow was measured by ocular blood flow tonography. Changes in blood pressure, heart rate, retinal venous blood flow, retinal capillary blood flow, optic nerve head blood flow, intraocular pressure and pulsatile ocular blood flow were detected from measurements taken at baseline and at 90 to 120 minutes following the instillation. Results: Intraocular pressure decreased significantly in both eyes. Retinal capillary blood flow increased significantly in both eyes. Optic nerve head blood flow increased significantly in treated eyes but remained unchanged in placebo eyes. There were no significant changes in retinal venous blood flow or pulsatile ocular blood flow in either eyes. Conclusion: Our results suggest that one administration of levobunolol may increase the retinal and optic nerve circulation but does not decrease the choroidal circulation.

Dilute Topical Proparacaine for Pain Relief after Photorefractive Keratectomy

The purpose of the study is to determine whether there is a nonanesthetic and nontoxic concentration of topical proparacaine that can be applied repeatedly to the cornea to reduce pain after photorefractive keratectomy (PRK). Part I: To determine a nonanesthetic concentration, the corneal sensitivity of 50 healthy volunteers was assessed using aesthesiometry before and after a drop of either 0.01%, 0.025%, 0.05%, 0.1%, or 0.2% topical proparacaine. Ten volunteers similarly were tested with multiple doses of 0.05% proparacaine. To evaluate toxicity, ten healthy volunteers self-administered 0.05% proparacaine to one eye and placebo to the other eye every 15 minutes for 12 hours on day 1 and every hour for 12 hours on days 2 through 7. Subjects were assessed throughout the week using visual acuity, slitlamp examination, aesthesiometry, and ultrasonic pachometry. Part II: In a prospective, double-masked study, 34 patients who underwent PRK (48 eyes) self-administered either topical 0.05% proparacaine or placebo for 1 week after PRK as needed to reduce pain. Patients recorded their pain score before and after drop use and answered a pain-relief questionnaire. Part I: Proparacaine concentrations greater than or equal to 0.1% eliminated sensation from some corneas; concentrations of less than or equal to 0.05% were never fully anesthetic. No corneal toxicity was observed except for some minimal punctate staining in both treatment and placebo eyes. Part II: Patients in the treatment group had significantly more pain relief (P < 0.001) for a longer period (P < 0.001) than did patients in the control group. Average change in pain score was significantly greater in the treatment group (P < 0.002). No significant difference in the number of days needed to reach complete epithelial healing was found between the two groups (P < 0.18). Dilute (0.05%) topical proparacaine is nonanesthetic and nontoxic, and can be used safely for at least 1 week to reduce pain after PRK.

CYSTEAMINE EYEDROPS DISSOLVE CORNEAL CRYSTALS IN YOUNG PATIENTS WITH NEPHROPAT11IC CYSTINOSIS

In nephropathic cystinosis, corneal cyatine crystals are present by one year of age and increase in density with time. The crystals are blamed for the photophobia and corneal erosions which plague older patients. He studied the safety and efficacy of eyedrops containing cysteamine, a cystine-depleting agent, in dissolving corneal crystals. First, cystinotic corneal stromal cells, cultured from a penetrating keratoplasty specimen, were depleted of 82% of their cystine by 1 mM cysteamine within 30 min. Second, rabbits treated for 8h per day for 3 weeks with 50 mM cysteamine eyedrops in a placebo-controlled, masked study exhibited no toxicity. Third, two cystinotic children (<2 years old) received cysteamine eyedrops (10 mM, hourly while awake) in a double-masked, placebo controlled trial. Normal saline was put in the opposite eye. In both children, biomicroscopic examination and silt lamp photography documented : a) Bilateral increase of crystals in the cornea between the start of oral cysteamine and the start of the eyedrop protocol; b) Nearly complete clearing of crystals from the cysteamine-treated corneas after 4-5 months of eyedrops; c) Progression or lack of regression in the corneas not treated with cysteamine. No toxicity was observed, and we are now treating the placebo eyes with cysteamine and enrolling older patients. This represents the first in vivo demonstration of crystal dissolution by cysteamine in cystinosis, and suggests that oral cysteamine, if adequately delivered to target tissues, might dissolve crystals in other cystinotic organs also.