Assessment of non-invasive tear break-up time and tear meniscus height after instillation of three different formulations of anesthetic eye drops by Oculus Keratograph 5M / Avaliação do tempo de ruptura lacrimal não invasivo e da altura do menisco lacrimal após a instilação de três diferentes formulações de colírio anestésico por Oculus Keratograph 5M

Abstract Purpose: To assess the non-invasive tear break-up time (NITBUT) and tear meniscus height (TMH) after instilling the three different types of anesthetic eye drops by Oculus Keratograph 5M. Methods: In this prospective study, 85 healthy subjects (85 eyes) were randomly divided into three groups. The groups were randomly received lidocaine hydrochloride 2%, proparacaine hydrochloride 0.5%, and tetracaine hydrochloride 0.5%. The qualitative and quantitative parameters of tear film were assessed using NITBUT and TMH, respectively. In all groups, the quantity of tear film using TMH was measured in the right eye of subjects, while the quality of tear film using NITBUT was assessed in the left eye. The analysis of variance (ANOVA) was used to compare the difference between before and after the intervention. A P-value < 0.05 was considered significant. Results: Differences for TMH and NITBUT between before and after applying lidocaine hydrochloride 2% were not statistically significant (P > 0.05). The mean values of NITBUT and TMH after the instillation of proparacaine hydrochloride 0.5% showed a significant decrease than before the intervention (P < 0.05). Also, after the use of tetracaine hydrochloride 0.5%, the mean value of NITBUT was significantly increased (P < 0.05), but the mean value of TMH was significantly decreased than before the intervention (P < 0.05). Conclusion: Our study showed that lidocaine hydrochloride 2% as an anesthetic eye drops can be an appropriate choice for eye examinations due to a lack of significant effect on the quantity and quality of tear film.

Resumo Objetivo: Avaliar o tempo de ruptura lacrimal não invasivo (NITBUT) e a altura do menisco lacrimal (TMH) após instilar os três tipos diferentes de colírio anestésico pelo Oculus Keratograph 5M. Métodos: Neste estudo prospectivo, 85 indivíduos saudáveis (85 olhos) foram divididos aleatoriamente em três grupos. Os grupos receberam aleatoriamente cloridrato de lidocaína a 2%, cloridrato de proparacaína a 0.5% e cloridrato de tetracaína a 0.5%. Os parâmetros qualitativos e quantitativos do filme lacrimal foram avaliados utilizando NITBUT e TMH, respectivamente. Em todos os grupos, a quantidade de filme lacrimal utilizando TMH foi medida no olho direito dos sujeitos, enquanto a qualidade do filme lacrimal usando NITBUT foi avaliada no olho esquerdo. A análise de variância (ANOVA) foi utilizada para comparar a diferença entre antes e depois da intervenção. Um valor de P < 0.05 foi considerado significativo. Resultados: Diferenças para TMH e NITBUT entre antes e depois da aplicação de cloridrato de lidocaína a 2% não foram estatisticamente significantes (P > 0.05). Os valores médios de NITBUT e TMH após a instilação de cloridrato de proparacaína a 0.5% mostraram uma diminuição significativa do que antes da intervenção (P < 0.05). Além disso, após o uso de cloridrato de tetracaína a 0.5%, o valor médio de NITBUT foi significativamente aumentado (P < 0.05), mas o valor médio de TMH foi significativamente menor do que antes da intervenção (P < 0.05). Conclusão: Nosso estudo mostrou que o cloridrato de lidocaína a 2% como colírio anestésico pode ser uma escolha apropriada para exames oftalmológicos devido à falta de efeito significativo sobre a quantidade e a qualidade do filme lacrimal.

Proparacaine-Induced Mydriasis During Strabismus Surgery.

AIM: To evaluate the mydriatic effect of proparacaine hydrochloride (PH) in children undergoing strabismus surgery under general anesthesia (GA). METHODS: This was a pilot, prospective, non-randomized, self-controlled interventional study. Nine children with esotropia or exotropia undergoing horizontal muscle squint surgery under GA at a tertiary eye care center were included. The six Group 1 patients underwent both eye surgeries, while the three Group 2 patients underwent single eye surgery. PH was instilled in one eye of Group 1 patients and both eyes of Group 2 patients. Change in pupil diameter (PD) was analyzed as the main outcome measure. RESULTS: Mean age of the patients was 4.67 ± 2.64 years. In the study eyes, mean average baseline PD was 1.59 ± 0.40 mm (range: 1.06-2.37), while postoperative average PD was 3.99 ± 1.34 mm (range: 1.79-6.02). The mean baseline PC had increased from 5.51 ± 1.09 mm to 12.6 ± 3.58 mm at the end of the surgery. PD and PC increased in all of the study eyes while no change in PD or PC was seen in the control eyes of either of the groups. The dilated pupil was skewed horizontally towards the muscle being operated upon in all of the study eyes. CONCLUSIONS: PH has a mydriatic effect of its own. It penetrates through the bare sclera and leads on to skewed dilation of the pupil. Surgeons should consider this effect while judging pupil alignment at the end of the surgery.

Corneal sensitivity following lacrimal gland excision in the rat.

PURPOSE: Dry eye disease (DED) produces ocular pain and irritation, yet a detailed characterization of ocular sensitivity in a preclinical model of DED is lacking. The aim of the present study was to assess nociceptive behaviors in an aqueous tear deficiency model of DED in the rat. METHODS: Spontaneous blinking, corneal mechanical thresholds, and eye wipe behaviors elicited by hypertonic saline (5.0 M) were examined over a period of 8 weeks following the unilateral excision of either the exorbital lacrimal gland or of the exorbital and infraorbital lacrimal glands, and in sham surgery controls. The effect of topical proparacaine on spontaneous blinking and of systemic morphine (0.5-3.0 mg/kg, subcutaneous [SC]) on spontaneous blinking and eye wipe responses were also examined. RESULTS: Lacrimal gland excision resulted in mechanical hypersensitivity and an increase in spontaneous blinking in the ipsilateral eye over an 8-week period that was more pronounced after infra- and exorbital gland excision. The time spent eye wiping was also enhanced in response to hypertonic saline (5.0 M) at both 1- and 8-week time-points, but only in infra- and exorbital gland excised animals. Morphine attenuated spontaneous blinking, and the response to hypertonic saline in dry eye animals and topical proparacaine application reduced spontaneous blinking down to control levels. CONCLUSIONS: These results indicate that aqueous tear deficiency produces hypersensitivity in the rat cornea. In addition, the increase in spontaneous blinks and their reduction by morphine and topical anesthesia indicate the presence of persistent irritation elicited by the activation of corneal nociceptors.

Antibacterial activity of preservative-free topical anesthetic drops in current use in ophthalmology departments.

AIM: The antibacterial effect of topical anesthetics may lead to false-negative cultures from corneal specimens of bacterial keratitis. This in vitro study compared the antibacterial effect of 3 unpreserved topical anesthetics to indicate the most appropriate agent for corneal scrapes. METHODS: Four bacterial strains (Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus pneumoniae) derived from the most frequently isolated microorganisms from corneal ulcers were cultured from stored control stocks and clinical specimens. These strains were used to determine the minimum inhibitory concentration (MIC) of 3 preservative-free anesthetic eyedrops: proxymetacaine 0.5%, oxybuprocaine 0.4%, and tetracaine 1%. RESULTS: There was no inhibition of growth seen with proxymetacaine 0.5% (5000 microg/mL) with any of the organisms except S. epidermidis, which demonstrated an MIC of 2500 microg/mL (equivalent to a dilution of (1/2)). Tetracaine 1% (10,000 microg/mL) produced an MIC ranging between 625 and 1250 microg/mL, inhibiting all 4 strains at the commercially available dilution. Oxybuprocaine 0.4% (4000 microg/mL) resulted to be the second most inhibitory preparation with an MIC ranging between 1000 and 2000 microg/mL. CONCLUSIONS: Currently used preservative-free topical anesthetics differ in bacterial growth inhibition. This in vitro study showed that proxymetacaine 0.5% is the least inhibitory on bacterial growth and therefore the most appropriate to be used before corneal scrapes.

Protein kinase C-delta mediates neuronal apoptosis in the retinas of diabetic rats via the Akt signaling pathway.

OBJECTIVE: Protein kinase C (PKC)-delta, an upstream regulator of the Akt survival pathway, contributes to cellular dysfunction in the pathogenesis of diabetes. Herein, we examined the role of PKC-delta in neuronal apoptosis through Akt in the retinas of diabetic rats. RESEARCH DESIGN AND METHODS: We used retinas from 24- and 35-week-old male Otsuka Long-Evans Tokushima fatty (OLETF) diabetic and Long-Evans Tokushima Otsuka (LETO) nondiabetic rats. To assess whether PKC-delta affects Akt signaling and cell death in OLETF rat retinas, we examined 1) PKC-delta activity and apoptosis; 2) protein levels of phosphatidylinositol 3-kinase (PI 3-kinase) p85, heat shock protein 90 (HSP90), and protein phosphatase 2A (PP2A); 3) Akt phosphorylation; and 4) Akt binding to HSP90 or PP2A in LETO and OLETF retinas in the presence or absence of rottlerin, a highly specific PKC-delta inhibitor, or small interfering RNAs (siRNAs) for PKC-delta and HSP90. RESULTS: In OLETF retinas from 35-week-old rats, ganglion cell death, PKC-delta and PP2A activity, and Akt-PP2A binding were significantly increased and Akt phosphorylation and Akt-HSP90 binding were decreased compared with retinas from 24-week-old OLETF and LETO rats. Rottlerin and PKC-delta siRNA abrogated these effects in OLETF retinas from 35-week-old rats. HSP90 siRNA significantly increased ganglion cell death and Akt-PP2A complexes and markedly decreased HSP90-Akt binding and Akt phosphorylation in LETO retinas from 35-week-old rats compared with those from nontreated LETO rats. CONCLUSIONS: PKC-delta activation contributes to neuro-retinal apoptosis in diabetic rats by inhibiting Akt-mediated signaling pathways.

The survival of herpes simplex virus in multidose office ophthalmic solutions.

PURPOSE: To determine the survival of herpes simplex virus type 1 (HSV-1) in several multidose ophthalmic solutions. METHODS: In three separate trials, 10 aliquots of 5 ml each of three common multidose topical ophthalmic solutions, sodium fluorescein, proparacaine, and nonpreserved artificial tears, were inoculated with 10(5), 10(4), and 10(3) pfu per ml of HSV-1. All samples were titered on A549 cells at various time points for surviving HSV-1. RESULTS: Herpes simplex virus type 1 was not recovered from the fluorescein and proparacaine solutions at 1 hour or any time thereafter, regardless of inoculation titer. Herpes simplex virus type 1 was recovered from the artificial tears up to 7 days. CONCLUSION: Unlike adenovirus, HSV-1 does not survive in preserved fluorescein and proparacaine multidose solutions; therefore, office transmission is highly unlikely.

Eledoisin and lacrimal secretion in the rabbit.

Eledoisin has been tried as a possible treatment for dry eye based on the hypothesis that it pharmacologically stimulates tear secretion when topically applied to the eye. To determine if topically applied eledoisin pharmacologically stimulates orbital lacrimal secretion, the orbital lacrimal gland excretory duct of normal rabbits was cannulated, and eledoisin was applied topically with and without prior administration of proparacaine. To determine if topically applied eledoisin stimulated accessory lacrimal gland secretion, isotonic buffer with and without eledoisin was tested in a rabbit model with only accessory lacrimal tissue remaining after the administration of proparacaine. Topically applied eledoisin did not pharmacologically stimulate lacrimal secretion but rather increased lacrimal gland secretion only in non-anesthetized eyes through a sensory reflex mechanism that is blocked by proparacaine.

Comparison of proteins in lacrimal gland fluid secreted in response to different stimuli.

To determine if different stimuli cause secretion of different proteins in lacrimal gland fluid (LGF), rabbits were anesthetized and LGF collected under baseline conditions (with the local anesthetic proparacaine), with ocular reflexes present, and in response to arterial injection of the cholinergic agonist acetylcholine (ACh) or the peptide vasoactive intestinal peptide (VIP). Proteins in LGF were separated by nondenatured gradient polyacrylamide gel electrophoresis. Except for minor differences, the number, the approximate molecular weights, and the amounts were the same in LGF secreted in response to four different stimuli. We concluded that the different stimuli caused protein release either from the same secretory cells or from different populations of secretory cells with the same secretory proteins.

Tear evaporimeter for measuring water evaporation rate from the tear film under controlled conditions in humans.

The rate of water evaporation from the tear film depends on the conditions under which it is determined. If measured in a controlled and easily reproducible setting, tear evaporation rate could serve as a useful diagnostic and research tool. We have developed a tear evaporimeter that provides a non-invasive method for evaluating water evaporation rate in eyes with normal or pathologic tear films. The subject is fitted with a pair of swimmer's goggles modified so that the air over the test eye is conditioned to a desired baseline of relative humidity (29.5%) and temperature (23 +/- 1 degree C). To eliminate other sources of water, the lids and skin under the goggles are covered with petroleum jelly. The subject is asked to keep his/her eye open and to avoid blinking during the 1-min test. The increase in relative humidity due to water evaporation from the tears is then determined. The surface area of the eye exposed to evaporation is calculated from the lid aperture. We measured the water evaporation rate in 52 normal eyes (average = 4.07 X 10(-7) +/- 0.40 X 10(-7) g/cm2/sec) and compared the results with values obtained in 52 eyes with various tear-film abnormalities (average = 8.17 X 10(-7) +/- 2.65 X 10(-7) g/cm2/sec). The difference between the two groups is statistically significant (P less than 0.01). In normal eyes, after the instillation of one drop of 0.5% proparacaine, the increase in evaporation rate was statistically significant.