Increased drug concentration and repeated eye drop administration as strategies to optimize topical drug delivery: A fluorophotometric study in healthy dogs.

OBJECTIVES: Determine tear film kinetics with different fluorescein concentrations and repeated eye drop administration at various time intervals. ANIMALS STUDIED: Six healthy Beagles. PROCEDURES: Six experiments were conducted on separate days: single eye drop administration (control) or two separate eye drops administered at 30 s, 1, 2, 5, and 10 min intervals. For each experiment, one eye received 0.3% fluorescein solution while the other eye received 1% fluorescein solution, and tear fluid was collected with capillary tubes at 0, 1, 5, 10, 20, 30, 40, 50, 60, 90, 120, and 180 min. Fluorescein concentrations were measured using automated fluorophotometry. RESULTS: Compared with 0.3% solution, eyes receiving 1% fluorescein solution had significantly higher tear film concentrations (p ≤ .046) and the area-under-the-fluorescein-time curve was twofold greater (p = .005). Compared with control: (i) Tear film concentrations were significantly higher for up to 20 min when repeating administration 30 s to 5 min after the first drop (p ≤ .006); (ii) The highest increase in area-under-the-curve was obtained with 2 and 5 min intervals for 0.3% (+109%-130%) and 1% solutions (+153%-157%); (iii) The highest increase in median precorneal retention time (defined as tear film concentration < 5% from baseline values) was obtained with 5 min intervals for 0.3% (55 min vs. 15 min in control) and 2-5 min intervals for 1% solutions (50 min vs. 25 min in control). CONCLUSIONS: Drug delivery to the ocular surface can be enhanced by using more concentrated formulations and/or by repeating eye drop administration 2-5 min after the first dose.

Precorneal retention time of ocular lubricants measured with fluorophotometry in healthy dogs.

OBJECTIVE: Determine the precorneal retention time of five different ocular lubricants commonly used in dogs. ANIMALS STUDIED: Six healthy Beagle dogs (n = 12 eyes). PROCEDURES: Five ocular lubricants were studied: Artificial Tears Solution® (1.4% polyvinyl alcohol), I-Drop® Vet Plus (0.25% hyaluronate), Optixcare® Eye Lube Plus (0.25% hyaluronate), Systane® Ultra (0.4% polyethylene glycol 400 and 0.3% propylene glycol), and Artificial Tears Ointment® (mineral oil/white petrolatum). Each lubricant was mixed with 10% sodium fluorescein to achieve 1% fluorescein formulations. Following topical administration of 35 mg in each eye, tear fluid was collected with capillary tubes at selected times (0, 1, 5, 10, 20, 30, 40, 50, 60, 90, 120, 180 min) and fluorescein concentrations were measured with a computerized scanning ocular fluorophotometer. RESULTS: Tear fluorescence was significantly greater with Artificial Tears Ointment® compared with other lubricant formulations from 1 to 20 min post-administration. Median (range) precorneal retention times were significantly different among the 5 lubricants, ranging from 40 minutes (20-90 min) for Artificial Tears Ointment®, 35 min (20-90 min) for Systane® Ultra, 30 min (10-60 min) for I-Drop® Vet Plus, 25 min (10-60 min) for Optixcare® Eye Lube Plus, and 10 min (10-20 min) for Artificial Tears Solution®. Precorneal retention time was significantly lower for Artificial Tears Solution® compared with the other 4 formulations. CONCLUSIONS: This study established normative data for the retention time of common lubricants on the ocular surface of dogs, which may be used to guide clinicians with their choice of lubricant and frequency of administration.

Topical Recombinant Human Nerve Growth Factor (Cenegermin) for Neurotrophic Keratopathy: A Multicenter Randomized Vehicle-Controlled Pivotal Trial.

PURPOSE: To evaluate the efficacy and safety of topical cenegermin (recombinant human nerve growth factor) in patients with neurotrophic keratopathy. DESIGN: Multicenter, randomized, double-masked, vehicle-controlled trial. PARTICIPANTS: Patients with neurotrophic persistent epithelial defect with or without stromal thinning. METHODS: The NGF0214 trial, conducted among 11 sites in the United States, randomized 48 patients 1:1 to cenegermin 20 µg/ml or vehicle eye drops, 6 drops daily for 8 weeks of masked treatment. Follow-up was 24 weeks. Safety was assessed in all patients who received study drug. Efficacy was assessed by intention to treat. MAIN OUTCOME MEASURES: The primary end point was healing of the neurotrophic lesion (persistent epithelial defect or corneal ulcer) after 8 weeks of masked treatment. Masked central readers measured neurotrophic lesions in randomized clinical pictures, then assessed healing status conventionally (<0.5 mm of fluorescein staining in the greatest dimension of the lesion area) and conservatively (0-mm lesion staining and no other residual staining). Secondary variables included corneal healing at 4 weeks of masked treatment (key secondary end point), overall changes in lesion size, rates of disease progression, and changes in visual acuity and corneal sensitivity from baseline to week 8. RESULTS: Conventional assessment of corneal healing showed statistically significant differences at week 8: compared to 7 of 24 vehicle-treated patients (29.2%), 16 of 23 cenegermin-treated patients (69.6%) achieved less than 0.5 mm of lesion staining (+40.4%; 95% confidence interval [CI], 14.2%-66.6%; P = 0.006). Conservative assessment of corneal healing also reached statistical significance at week 8: compared to 4 of 24 vehicle-treated patients (16.7%), 15 of 23 cenegermin-treated patients (65.2%) achieved 0 mm of lesion staining and no other residual staining (+48.6%; 95% CI, 24.0%-73.1%; P < 0.001). Moreover, the conservative measure of corneal healing showed statistical significance at week 4 (key secondary end point). Compared to vehicle, cenegermin-treated patients showed statistically significant reductions in lesion size and disease progression rates during masked treatment. Cenegermin was well tolerated; adverse effects were mostly local, mild, and transient. CONCLUSIONS: Cenegermin treatment showed higher rates of corneal healing than vehicle in neurotrophic keratopathy associated with nonhealing corneal defects.

Parameter Estimation for Evaporation-Driven Tear Film Thinning.

Many parameters affect tear film thickness and fluorescent intensity distributions over time; exact values or ranges for some are not well known. We conduct parameter estimation by fitting to fluorescent intensity data recorded from normal subjects' tear films. The fitting is done with thin film fluid dynamics models that are nonlinear partial differential equation models for the thickness, osmolarity and fluorescein concentration of the tear film for circular (spot) or linear (streak) tear film breakup. The corresponding fluorescent intensity is computed from the tear film thickness and fluorescein concentration. The least squares error between computed and experimental fluorescent intensity determines the parameters. The results vary across subjects and trials. The optimal values for variables that cannot be measured in vivo within tear film breakup often fall within accepted experimental ranges for related tear film dynamics; however, some instances suggest that a wider range of parameter values may be acceptable.

Ocular surface involvement in patients with neurofibromatosis type 1 syndrome.

PURPOSE: The aim of this study is to evaluate ocular surface morphological and functional changes in patients with neurofibromatosis type 1 (NF1). METHODS: Twenty-eight patients with NF1 and 14 healthy subjects were included in this study. All participants underwent a medical history collection, a complete ophthalmological examination including slit lamp exam and assessment of best-corrected visual acuity (BCVA), corneal sensitivity, and lacrimal function (Schirmer test and fluorescein tear break-up time test). Corneal nerves' morphology and endothelial cells density were evaluated by in vivo corneal confocal microscopy (IVCM). Tear and conjunctiva epithelium samples were collected to evaluate nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) tear levels and conjunctival expression of their receptors TrkA and p75NTR. RESULTS: Patients with NF1 showed a significant decrease of FTBUT when compared with healthy subjects (p < 0.001). Corneal sensitivity was ≤ 50 mm in 46% of NF1 patients. IVCM showed a significant increase of corneal nerve branching and of corneal endothelial cells density. No significant difference was observed between the two groups on NGF and BDNF tear levels and conjunctival expression of their receptors. CONCLUSION: This study demonstrated the presence of ocular surface changes in NF-1 patients including decrease of tear stability and of corneal sensitivity. Patients with NF1 also showed changes of corneal endothelial cells' density.

Corneal Health during Three Months of Scleral Lens Wear.

SIGNIFICANCE: This study evaluated the effects scleral lens wear has on corneal health using fluorometry and in vivo confocal microscopy. No subclinical changes on healthy corneas of young subjects were observed during 3 months of scleral lens wear. PURPOSE: This study aimed to evaluate the effects 3 months of scleral lens wear has on the corneal epithelial barrier function, dendritic cell density, and nerve fiber morphology. METHODS: Twenty-seven neophytes (mean [standard deviation] age, 21.4 [3.9] years) wore scleral lenses of a fluorosilicone acrylate material bilaterally (97 Dk, 15.6 to 16.0-mm diameter) for 3 months without overnight wear. Subjects were randomized to use either Addipak (n = 12) or PuriLens Plus (n = 15) during lens insertion. Measurements of corneal epithelial permeability to fluorescein were performed with automated scanning fluorophotometer (Fluorotron Master; Ocumetrics, Mountain View, CA) on the central cornea of the right eye and the temporal corneal periphery of the left eye. Images of the distributions of corneal nerve fibers and dendritic cells and nerve fibers were captured in vivo with a confocal laser scanning microscope (Heidelberg Retina Tomograph, Rostock Cornea Module; Heidelberg Engineering, Heidelberg, Germany) on the central and inferior peripheral cornea of the left eye. Corneal measurements and imaging were performed at baseline and after 1 and 3 months of lens wear. RESULTS: The corneal permeability values in natural log, dendritic cell densities, and nerve fiber morphology did not significantly change from baseline to 1 and 3 months of lens wear, for both central and peripheral corneal regions (P > .05). Dendritic cell density at the inferior cornea was higher than the central cornea throughout the study (P < .001). No relationships were observed between each outcome measurements and the saline solution groups (P > .05). CONCLUSIONS: Scleral lens wear for 3 months on healthy cornea of young subjects did not affect corneal epithelial barrier function, nerve fiber, and dendritic cell densities. Buffered and nonbuffered saline solutions impacted the corneal health in similar ways.

Impact of acute conjunctivitis on ocular surface homeostasis in dogs.

OBJECTIVE: To investigate the effects of acute conjunctivitis on tear film characteristics and corneal sensitivity in dogs. ANIMALS STUDIED: Eight female spayed Beagle dogs (1.5-2 years old, 7.5-10 kg). PROCEDURES: On two consecutive days, one randomly selected eye in each dog received 1 or 375 mg/mL histamine solution to induce mild or severe conjunctivitis, while the contralateral eye served as control. Diagnostic tests were performed in the following order: fluorescein instillation and repeated tear collection over 20 minutes (to determine tear volume [TV] and turnover rate [TTR] by fluorophotometry), Schirmer tear test-1 (STT-1), tear ferning, corneal esthesiometry, and tear film breakup time (TFBUT). RESULTS: Results are presented as median values for severe conjunctivitis, mild conjunctivitis, and control eyes. Eyes with severe conjunctivitis had significantly higher STT-1 (24, 19.5, 17.5 mm/min; P = .002) and significantly lower TFBUT (10.5, 13.5, 15.5 s; P = .002), but no changes were noted in corneal tactile sensation (2, 2.5, 2.5 cm) or tear ferning (grades 2, 2, 2.5). Severe conjunctivitis significantly increased TV by nearly 10-fold (631, 97, 65 µL) initially (reflex tearing), although basal TV returned rapidly (<5 minutes) in all eyes (46, 58, 48 µL). Finally, there was a nonsignificant trend for higher reflex TTR in the conjunctivitis vs control eyes (68, 58, 43%/min). CONCLUSIONS: Experimentally induced conjunctivitis increases tear quantity and decreases tear quality in dogs, but has no impact on corneal sensitivity. Changes in tear film dynamics could affect ocular pharmacology (eg, precorneal retention time), although homeostasis of lacrimal volume and drainage is rapidly restored.

A study of dry eye after cataract surgery in MGD patients.

OBJECTIVE: To investigate the dry eye symptoms after cataract surgery in MGD patients and their relationships METHODS: The study included 115 patients (115 eyes) with age-related cataract that underwent uncomplicated cataract surgery, and the patients were divided into two groups according to the MGD diagnostic criteria: group A (MGD group) and group B (control group). Schirmer I test (ST-I), tear breakup time (TBUT), and corneal fluorescein staining (CFS) were performed preoperatively and at 3 days, 7 days, 14 days, and 30 days postoperatively. We also measured eyelid meibomian gland morphology, meibomian gland expression, and meibum character scores before and after the cataract surgery. RESULTS: Postoperatively, in group A, TBUT decreased and CFS scores increased significantly. ST-I increased in the early postoperative course but decreased later. The eyelid margin morphology scores and meibomian gland expression scores of group A significantly increased after the cataract operation. Thus, patients with MGD may have a greater chance of developing the dry eye disease after cataract surgery. Cataract surgery may aggravate the signs of MGD, and the severity of MGD may positively correlate with TBUT, CFS, and corneal lesions after surgery. CONCLUSIONS: The characteristics of dry eye after cataract surgery in patients with MGD are different from common cataract patients, changes in the early postoperative phase to the ocular surface were caused by surgical factors, and the damages to epithelial function in the later postoperative phase were mainly associated with the inflammation of the meibomian gland and eyelid.

Rapid and visual detection of berberine hydrochloride based on a water-soluble pyrene derivative.

In this study, a rapid method for the detection of berberine hydrochloride (BRH) was developed based on a water-soluble pyrenyl probe, 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS). This method features low cost, good selectivity, high sensitivity and a fast response. The sensing mechanism of this probe is attributed to the formation of a complex between HPTS and BRH induced by electrostatic interaction and π-π stacking. To the best of our knowledge, this is the first fluorescent sensor for BRH based on organic materials that has low cost and a visual response. The detection limit of this method was as low as 1.24 µM and the linear response range is 2-50 µM. This method also allowed rapid detection of BRH real samples.

Calibration of an in-water multi-excitation fluorometer for the measurement of phytoplankton chlorophyll-a fluorescence quantum yield.

A multi-excitation fluorometer (MFL, JFE Advantech Co., Ltd.), originally designed to discriminate between phytoplankton species present within a population, has been redirected for use in fluorescence quantum yield (FQY) determination. While this calibration for apparent FQY requires no modification of the MFL, it is necessary to have an independent measurement of the spectral absorption coefficient of the subject fluid. Two different approaches to calibration were implemented. The primary method made use of reference fluorescent dye solutions of known quantum yield. The second method made use of acrylic fluorescent plaques and films. The two methods yielded consistent results, except in the 570 and 590 nm LED channels of the MFL. Application of the MFL in FQY determination is illustrated with an in situ Southern Ocean sample.

An Automated Grading and Diagnosis System for Evaluation of Dry Eye Syndrome.

This article describes methods used to determine the severity of Dry Eye Syndrome (DES) based on Oxford Grading Schema (OGS) automatically by developing and applying a decider model. The number of dry punctate dots occurred on corneal surface after corneal fluorescein staining can be used as a diagnostic indicator of DES severity according to OGS; however, grading of DES severity exactly by carefully assessing these dots is a rather difficult task for humans. Taking into account that current methods are also subjectively dependent on the perception of the ophtalmologists coupled with the time and resource intensive requirements, enhanced diagnosis techniques would greatly contribute to clinical assessment of DES. Automated grading system proposed in this study utilizes image processing methods in order to provide more objective and reliable diagnostic results for DES. A total of 70 fluorescein-stained cornea images from 20 patients with mild, moderate, or severe DES (labeled by an ophthalmologist in the Keratoconus Center of Yildirim Beyazit University Ataturk Training and Research Hospital) used as the participants for the study. Correlations between the number of dry punctate dots and DES severity levels were determined. When automatically created scores and clinical scores were compared, the following measures were observed: Pearson's correlation value between the two was 0.981; Lin's Concordance Correlation Coefficients (CCC) was 0.980; and 95% confidence interval limites were 0.963 and 0.989. The automated DES grade was estimated from the regression fit and accordingly the unknown grade is calculated with the following formula: Gpred = 1.3244 log(Ndots) - 0.0612. The study has shown the viability and the utility of a highly successful automated DES diagnostic system based on OGS, which can be developed by working on the fluorescein-stained cornea images. Proper implemention of a computationally savvy and highly accurate classification system, can assist investigators to perform more objective and faster DES diagnoses in real-world scenerios.

Effect of Povidone Iodine 5% on the Cornea, Vision, and Subjective Comfort.

PURPOSE: To determine the effects of povidone iodine 5% (Betadine 5%) applied to the eye on visual function, corneal integrity, and subjective complaints. METHODS: Ten subjects were chosen to participate in this study (average age 40.6 ± 19.6; age range 22-68). LogMAR acuity, contrast sensitivity, corneal fluorescein staining, and subjective complaints were measured before and after 60 µl of Betadine 5% or saline were applied to one eye (eligibility visit, baseline, 5, 30, and 60 minutes and 4 and 24 hours post-application). Contrast sensitivity at 14 cpd was determined with a spatial two-alternative, forced choice procedure (Beethoven software). The National Eye Institute (NEI) grid pattern was used to grade corneal staining with sodium fluorescein. To avoid the detrimental effects of sodium fluorescein administration on functional vision, the corneal staining baseline was measured at the eligibility visit. Subjective complaints were monitored using the Schein dry eye questionnaire. RESULTS: The data were analyzed with an ANOVA. Saline administration did not alter logMAR acuity, contrast sensitivity, corneal fluorescein staining, or subjective complaints at any visit. Betadine administration significantly reduced the logMAR acuity, compared to baseline and the saline data, at the 30- and 60-minute visits (all P values <.05). The contrast sensitivity was significantly reduced compared to the baseline and the saline results at 5, 30, and 60 minutes after Betadine application (all P values <.05). The Betadine significantly increased the Schein questionnaire score, compared both to baseline and the saline data, at the 1- and 4-hour visits (all P values <.05). Total corneal staining and the maximum NEI sector staining were significantly different from baseline and from the saline results at every visit (all P values <.05). CONCLUSIONS: Betadine 5% application significantly decreases epithelial integrity of the cornea, decreases functional vision, and increases subjective complaints.

The Relation of Ocular Surface Irregularity and Visual Disturbance in Early Stage Acanthamoeba Keratitis.

PURPOSE: To evaluate the relation between ocular surface irregularity and visual disturbance in early stage Acanthamoeba keratitis (AK). METHODS: Fifteen patients with culture-proven AK underwent routine ophthalmic examinations, including best-corrected visual acuity (BCVA) measurement, slitlamp biomicroscope examination, and corneal fluorescein dye staining test, in both the eyes. We also evaluated the corneal sensitivity with Cochet-Bonnet esthesiometer, tear functions by Schirmer's test, and ocular surface irregularity by corneal topography and compared the results with the contralateral healthy eyes in this study. RESULTS: The mean logarithm of the minimum angle of resolution BCVA (0.71±0.77) was significantly lower in the eyes with AK (P=0.002). Epithelial disorders were present in all eyes, and radial keratoneuritis in 14 eyes (93.3%). The mean corneal sensitivity (39.3±24.1 mm) was significantly lower in eyes with AK compared with the healthy eyes (P=0.005). The mean Schirmer's test value (22.5±12.0 mm) in eyes with AK was significantly higher compared with the healthy eyes (P=0.01). The ocular surface irregularity indices (the surface regularity index, 2.47±0.42; the surface asymmetry index, 3.24±1.31) were significantly higher in eyes with AK compared with contralateral healthy eyes (P<0.0001 and P<0.0001, respectively). CONCLUSIONS: The ocular surface disease in AK is associated with decrease in corneal sensitivity and increase in Schirmer's test value and ocular surface irregularity indices. The visual disturbance in AK may owe not only to corneal haze but also to ocular surface irregularity.

Multicenter Study of a Novel Topical Interleukin-1 Receptor Inhibitor, Isunakinra, in Subjects With Moderate to Severe Dry Eye Disease.

OBJECTIVES: Isunakinra, formerly known as EBI-005, is a novel interleukin (IL)-1 receptor inhibitor developed for topical treatment of patients with dry eye disease (DED). This phase 1b/2a multicenter, double-masked, randomized, vehicle controlled environmental trial assessed the safety and biological activity of isunakinra in patients with moderate to severe DED. METHODS: Subjects (N=74) were randomized to vehicle (placebo) or isunakinra (5 or 20 mg/mL) 3×/daily for 6 weeks. Evaluations included safety, tolerability, biological activity for signs (corneal fluorescein staining [CFS]), symptoms (pain or sore eyes and total Ocular Surface Disease Index [OSDI]), and reduction in rescue artificial tear use. RESULTS: Topical administration of isunakinra (5 and 20 mg/mL) was safe and well tolerated and resulted in clinically relevant improvements in symptoms (OSDI score, painful/sore eye component of OSDI) and signs (total CFS) compared with baseline with no dose response. OSDI scores improved from baseline by 38% (18.9 points) at 6 weeks and CFS scores improved by 33% (3 points) in the isunakinra groups. These changes were not statistically significant compared with the vehicle. Use of artificial rescue tears was significantly reduced in the isunakinra treatment groups (mean=9 vials) compared with vehicle (mean=31 vials). The differences between isunakinra and vehicle treatments were more pronounced in subjects with OSDI scores less than 50 at baseline. CONCLUSIONS: Isunakinra was safe, well tolerated and showed clinically meaningful improvements in signs and symptoms of DED. These results encouraged the design of an adequately powered study to characterize the safety and efficacy of isunakinra in ocular surface diseases.

Effects of Muller's muscle-conjunctival resection for ptosis on ocular surface scores and dry eye symptoms.

This article evaluates the effects of Muller's muscle-conjunctival resection (MMCR) on ocular surface scores and dry eye symptoms. Forty-six patients were enrolled in the study. Eighteen underwent bilateral upper eyelid skin excision with MMCR and 28 underwent bilateral upper eyelid skin-only excision (control group). The Salisbury Eye Evaluation Questionnaire and an ocular surface evaluation protocol consisting of Schirmer's test, tear break-up time (TBUT), fluorescein and rose bengal corneal staining were performed during the pre-operative consultation and on postoperative days 7, 30, and 90. Improvement in symptoms questionnaire scores from baseline was observed on postoperative day 90 in the blepharoplasty plus MMCR group. There was no change in questionnaire scores in patients who underwent blepharoplasty alone. No between-group difference in Schirmer's test, TBUT, or fluorescein and rose bengal staining was found at any time point. In the blepharoplasty-only (control group), the fluorescein staining score was reduced on postoperative day 30 as compared to baseline, but not on day 90. In this sample, addition of MMCR to upper eyelid blepharoplasty did not worsen ocular surface scores or dry eye symptoms.

New Grading System and Treatment Guidelines for the Acute Ocular Manifestations of Stevens-Johnson Syndrome.

PURPOSE: To describe a new grading system and associated treatment guidelines for the acute ocular manifestations of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). DESIGN: Prospective case series. PARTICIPANTS: Seventy-nine consecutive patients (158 eyes) evaluated and treated for acute ocular involvement in SJS or TEN during hospitalization. METHODS: Photographic and chart review of acute ocular findings, interventions received, and outcomes with regard to visual acuity, dry eye symptoms, and scarring sequelae at least 3 months after the acute illness. MAIN OUTCOME MEASURES: Visual acuity, dry eye severity, and scarring of the ocular surface and eyelids were assessed after follow-up of at least 3 months. RESULTS: Cases graded as mild or moderate were managed medically. All had best-corrected visual acuity (BCVA) of 20/20, no dry eye symptoms, and no scarring sequelae. Cases graded as severe or extremely severe were treated with urgent amniotic membrane transplantation (AMT) in addition to medical management. Severe cases all had BCVA of 20/20 and mild or no dry eye problems. Five of 28 patients had mild tarsal conjunctival scarring. No other scarring sequelae occurred. Nine of the 10 extremely severe cases had BCVA of 20/20 (1 was 20/30). Three of 10 had moderate scarring of the tarsal conjunctiva and lid margins and also moderate dry eyes with severe photophobia. Seven of 10 had only mild or no dry eye symptoms and scarring sequelae. CONCLUSIONS: This grading system facilitates decision making in the evaluation and management of the acute ocular manifestations of SJS and TEN. Mild and moderate cases have a low risk of significant scarring or visual sequelae and may be monitored and treated medically if not worsening. Severe and extremely severe cases should receive urgent AMT to decrease the risk of scarring and visual sequelae.

The Pre-Sac Reflux Test (PSRT): a new diagnostic test for presaccal stenosis/obstruction.

PURPOSE: To introduce a new procedure, the Pre-Sac Reflux Test (PSRT), to screen for epiphora caused by presaccal stenosis/obstruction, and to determine the reliability of this new test in the diagnosis of presaccal stenosis/obstruction. METHODS: A nonrandomized, prospective, comparative case series of 280 eyes of 140 patients with unilateral presaccal stenosis/obstruction was performed. The PSRT was performed by a masked examiner on both eyes of each patient. After fluorescein staining, the lower lid was everted and lower punctum was observed using a cobalt-blue filter under slit-lamp magnification. After blotting excess fluorescein on the punbtum, the area of lacrimal ampulla was massaged with mild pressure with an index finger. The reflux (billowing of the fluorescein-stained tear) from each lower punctum were compared, and the bilateral symmetry was measured. In the same way, reflux from each upper punctum were compared for bilateral symmetry. The PSRT was considered positive if reflux from punctum was absent, or reduced asymmetrically, compared with that from contralateral punctum. If the test of either upper or lower punctum showed positive, the eye was considered positive. The validity of PSRT was measured by sensitivity and specificity, as well as positive- and negative-predictive values. RESULTS: The PSRT used to diagnose presaccal stenosis/obstruction has a sensitivity of 92.9 % and a specificity of 97.1 %. It has a positive-predictive value of 97.0 % and a negative-predictive value of 93.2 %. CONCLUSIONS: The PSRT is a reliable screening test for diagnosis of presaccal stenosis/obstruction.

EXPERIMENTAL VISUALIZATION AND QUANTIFICATION OF VITREOUS CONTAMINATION FOLLOWING INTRAVITREAL INJECTIONS.

PURPOSE: To detect and quantify vitreous contamination after intravitreal injection using an experimental vitreous contamination model. METHODS: Enucleated porcine eyes served as a Type 1 experimental vitreous contamination model with fluoresbrite carboxylate microspheres applied to the conjunctival surface. Saline solution (0.05 mL) was injected using a 27-, 30-, or 32-gauge (G) needle. Injection procedures were monitored using an intraocular fiber catheter. Condensed microspheres were applied to an excised sheet of porcine sclera (Type 2 experimental vitreous contamination model). Saline solution (0.05 mL) was injected from the top of an applied condensed microsphere through the sclera using a needle of one of the aforementioned gauges, and samples were then collected. The fluorescence strength of samples was measured using fluorophotometry. RESULTS: We visually detected fluorescent microspheres in 10/10, 9/10, and 9/10 eyes injected with 27-G, 30-G, and 32-G needles, respectively. In the experimental quantification study, values at all needle gauges were significantly higher than those of controls (P < 0.01). Fluorescence strength was significantly higher in the 27-G group than in the 30- (P < 0.01) and 32-G (P < 0.01) groups. CONCLUSION: Intravitreal injection carries the risk of introducing contamination directly into the eyes even when a 32-G needle is used. Furthermore, the 27-G needle carries the highest contamination risk.

Corneal permeability changes in dry eye disease: an observational study.

BACKGROUND: Diagnostic tests for dry eye disease (DED), including ocular surface disease index (OSDI), tear breakup time (TBUT), corneal fluorescein staining, and lissamine staining, have great deal of variability. We investigated whether fluorophotometry correlated with previously established DED diagnostic tests and whether it could serve as a novel objective metric to evaluate DED. METHODS: Dry eye patients who have had established signs or symptoms for at least 6 months were included in this observational study. Normal subjects with no symptoms of dry eyes served as controls. Each eye had a baseline fluorescein scan prior to any fluorescein dye. Fluorescein dye was then placed into both eyes, rinsed with saline solution, and scanned at 5, 10, 15, and 30 min. Patients were administered the following diagnostic tests to correlate with fluorophotometry: OSDI, TBUT, fluorescein, and lissamine. Standard protocols were used. P < 0.05 was considered significant. RESULTS: Fifty eyes from 25 patients (DED = 22 eyes, 11 patients; Normal = 28 eyes, 14 patients) were included. Baseline scans of the dry eye and control groups did not show any statistical difference (p = 0.84). Fluorescein concentration of DED and normal patients showed statistical significance at all time intervals (p < 10(-5), 0.001, 0.002, 0.049 for 5, 10, 15, & 30 min respectively). Fluorophotometry values converged towards baseline as time elapsed, but both groups were still statistically different at 30 min (p < 0.01). We used four fluorophotometry scoring methods and correlated them with OSDI, TBUT, fluorescein, and lissamine along with adjusted and aggregate scores. The four scoring schemes did not show any significant correlations with the other tests, except for correlations seen with lissamine and 10 (p = 0.045, 0.034) and 15 min (p = 0.013, 0.012), and with aggregate scores and 15 min (p = 0.042, 0.017). CONCLUSIONS: Fluorophotometry generally did not correlate with any other DED tests, even though it showed capability of differentiating between DED and normal eyes up to 30 min after fluorescein dye instillation. There may be an aspect of DED that is missed in the current regimen of DED tests and only captured with fluorophotometry. Adding fluorophotometry may be useful in screening, diagnosing, and monitoring patients with DED.