Nasolacrimal Occlusion Research Articles

A Previsit Intervention’s Influence on Glaucoma Topics Discussed between Black Patients and Providers

The objectives of this study were to conduct a randomized controlled trial testing the effectiveness of a previsit glaucoma video/question prompt list intervention, and to examine the impact on how often providers educate Black patients about glaucoma and glaucoma medication topics during visits. A randomized controlled trial of a glaucoma question prompt list/video intervention. Black patients with a diagnosis of glaucoma who are taking 1 or more glaucoma medications and report being nonadherent. One hundred eighty-nine Black patients with glaucoma were enrolled and assigned to either a usual care or an intervention group where they watched a video emphasizing the importance of asking questions and received a glaucoma question prompt list to complete before clinic visits. Visits were audio-taped and patients were interviewed after visits. Whether the provider educates about different glaucoma and glaucoma medication topics. Patients in the intervention group were significantly more likely to ask providers 1 or more questions about glaucoma and its treatment. Providers were significantly more likely to educate intervention patients about their diagnosis (P= 0.001), intraocular pressure (P= 0.03), the likelihood of the need for long-term therapy (P= 0.001), and the physical changes associated with glaucoma (P= 0.001) than usual-care patients. Providers were also significantly more likely to educate intervention patients about the purpose of their medications (P= 0.03) and side effects (P= 0.001) than usual-care patients. Providers only educated 29% of patients about adherence (33% of intervention group patients and 25% of usual-care patients). Few providers educated patients about barriers and fears/concerns in using glaucoma medications, the cost of medications and insurance coverage, how to administer eye drops, and nasolacrimal occlusion. The intervention significantly increased provider education about many glaucoma and glaucoma medication topics. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Knowledge and practice of eye drops instillation technique in India: A survey of 396 optometrists

Abstract Aim: The aim of this article is to evaluate the knowledge about perfect eye drops instillation technique among optometrists in India. Materials and Methods: An online questionnaire-based, cross-sectional study was conducted. A self-administered, electronic questionnaire with a cover letter explaining the aim of the study was distributed among optometrists practicing in India. Demographic characteristics were summarized using descriptive statistics. Categorical variables were summarized using frequencies and percentages. Results: Among 396 respondents, 237 (59.84%) were females and 159 (40.16%) were males with a mean age of 24.5 ± 2.81 years. Two-fifths of the optometrists opted for washing hands before eye drop instillation. Similarly, almost nine-tenths of the participants preferred to instill eye drops asking patients to sit and about one-tenth of the optometrist preferred patients in supine position during administering drops. Most common errors during drop instillation among optometrists were drop instillation without nasolacrimal occlusion (19.95%) and hand hygiene (69.94%). Conclusion: Proper education and awareness about eye drop instillation process should be given to all eye care practitioners so that non-compliance and incorrect methods of drop instillation can either be minimized or nullified from patients’ end.

Subjective and objective assessment of the eye drop instillation technique: A hospital-based cross-sectional study.

Purpose:To objectively and subjectively evaluate eye drop technique and assess communicated instructions, and reported problems with eye drop instillation among tertiary care sample eye drop users.Methods:A cross-sectional, observational study was carried out among patients attending our outpatient clinic from June to September 2020. Eligible participants obtained through convenient sampling were assessed for their eye drop instillation performance. The objective evaluation was made using observation of a demonstration and subjective assessment through responses to an interview. Patient inclusion criteria were being aged ≥18 years and using eye drops for ≥ one month; excluded if having a disability in communication or physical barriers in using eye drops. The patient reported difficulties and previous education about the instillation were also obtained.Results:Participants (n = 84) had a mean age of 50.3 ± 14.0 years. During the demonstration, almost everyone (86.9%) successfully instilled at least one drop in the eye. None of the participants exhibited a perfect drop technique. The most common deviations were failing to close the eye (60.7%), touching the bottle to the eye or eyelid (36.9% of patients), and multiple blinks after drop instillation without nasolacrimal occlusion (25.0%). Forty percent of patients reported ≥1 problem and only a small sample recalled having had education in the eye drop instillation technique.Conclusion:Most participants failed to properly execute the eye drop technique. A proactive role of the prescribing practitioner to assess a patient’s ability to instill eye drops correctly could be helpful.

English

BACKGROUND Epiphora is a common annoying symptom, embarrassing the patient both socially and functionally and may even endanger the eye. Chronic Dacryocystitis is the most common cause of epiphora which arises from nasolacrimal duct occlusion. Dacryocystorhinostomy (DCR) is the procedure of choice in the management of Dacryocystitis. We wanted to study the final outcome following endonasal DCR for chronic dacryocystitis with or without using silicon stent, evaluate the causes of persistence of epiphora in patients with or without the use of lacrimal stents and identify the methods of overcoming them postoperatively. METHODS A case control study to compare the results of Endonasal DCR with and without stent was conducted among 96 patients of both genders aged above 20 years with symptoms and signs suggestive of nasolacrimal duct blockage. All the cases and controls were randomly selected and included as group A and group B. RESULTS 96 patients were included in this study and they were divided into two groups (Group A and Group B) with 48 patients in each group. More than 75 % of the patients were between 31 and 60 years of age with a mean age of 44.36 ± 3.15 years. In Group B, 72.91 % of the cases were between 31 and 60 years of age with a mean age of 45.50 ± 4.10 years. There was no statistically significant difference in both groups. In group A (DCR with stent) success rate or relief of symptoms was 96 % whereas in group B (DCR without stent) success rate or symptomatic relief was 80 %. CONCLUSIONS Endoscopic endonasal DCR with stent is a safe and minimally invasive procedure and is an effective treatment for patients who have failed primary endoscopic DCR without stent and also in cases of mucocele and pyocele of the sac. KEYWORDS Chronic Dacryocystitis, Dacryocysto-Rhinostomy, Nasolacrimal Duct and Endoscopic Dacryocysto-Rhinostomy

Eye drop technique and patient-reported problems in a real-world population of eye drop users.

To assess eye drop technique and patient-reported problems with eye drop instillation in a primary care sample of eye drop users. Cross-sectional observational study in 136 community pharmacies in Belgium. Patient inclusion criteria were being age ≥ 18 years and using eye drops for ≥ 1 month (to ensure that patients were already familiar with eye drop instillation). Participants demonstrated their eye drop technique and completed a self-administered questionnaire. Participants (n = 678) had a mean age of 68.9 ± 12.4 years. During the demonstration, almost everyone (98.0%) successfully instilled at least one drop in the eye, although 14% required multiple attempts to achieve this. Only 3% of the sample exhibited perfect drop technique, meaning that they performed correctly all the steps. Most common deviations were touching the bottle to the eye or eyelid (40.7% of patients), and failing to close the eye (67.8%) and perform nasolacrimal occlusion for at least 1 min (94.7%) after drop instillation. Importantly, we found that 20% of ophthalmic suspensions were not shaken before use. Forty percent of patients reported ≥ 1 problem with eye drop instillation. Most common problems were difficulties with getting a drop in the eye (18.3% of patients), too many drops coming out of the bottle (14.6%), and difficulty squeezing the bottle (12.2%). About half of the sample recalled having had education in eye drop instillation technique. This study showed suboptimal eye drop technique in real-world clinical practice. A proactive role of community pharmacists in detecting and resolving these problems could be helpful.

New technique to reduce systemic side effects of timolol eye drops: The tissue press method-Cross-over clinical trial.

Nasolacrimal occlusion (NLO) is effective in reducing systemic absorption of eye drop medication but it is difficult and often performed poorly. We propose an alternative easier and equally effective technique. To test the effectiveness of systemic absorption, we evaluated plasma concentration and ocular effects after topically administered timolol and compared to NLO. Cross-over trial carried out in Capital Eye Specialist, Wellington. A total of 21 subjects over 18 years without contraindications for topical beta-blocker medication and not using systemic beta-blockers. During three clinic visits separated by at least one week, alternative approaches to reduce systemic eye drop absorption were tested. These were: (a) nasolacrimal (punctal) occlusion for 5 min, (b) tissue press method or (c) no intervention. Timolol plasma levels were measured 1 h after drop application. At each visit, baseline measurement of blood pressure, heart rate and intraocular pressure (IOP) were performed, and repeated 1 h after timolol 0.5% eye drop application. Comparison of timolol plasma concentration after each intervention. Secondary outcome measurements included effects on blood pressure, heart rate and IOP. Plasma timolol concentrations after tissue press method and NLO were significantly lower than those without intervention. Comparing tissue press method to NLO, there were no significant differences in plasma levels of timolol, blood pressure, heart rate or IOP. The tissue press method is equally effective as NLO in reducing systemic absorption of timolol. It is also easier and faster to administer.

Topical medication instillation techniques for glaucoma.

Glaucoma is a leading cause of irreversible blindness worldwide and the second most common cause of blindness after cataracts. The primary treatment for glaucoma aims to lower intraocular pressure (IOP) with the use of topical medicines. Topical medication instillation techniques, such as eyelid closure and nasolacrimal occlusion when instilling drops, have been proposed as potential methods to increase ocular absorption and decrease systemic absorption of the drops. To investigate the effectiveness of topical medication instillation techniques compared with usual care or another method of instillation of topical medication in the management of glaucoma or ocular hypertension. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 12), MEDLINE Ovid (1946 to 8 December 2016), Embase Ovid (1947 to 8 December 2016), PubMed (1948 to 8 December 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 8 December 2016), International Pharmaceutical Abstracts Database (1970 to 8 December 2016), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched 13 May 2013), ClinicalTrials.gov (www.clinicaltrials.gov) (searched 8 December 2016) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) (searched 8 December 2016). We did not use any date or language restrictions in the electronic searches for trials. We included randomized controlled trials which had compared any topical medication instillation technique with usual care or a different method of instillation of topical medication. Two review authors independently screened records from the searches for eligibility, assessed the risk of bias, and extracted data. We followed methods recommended by Cochrane. We identified two trials (122 eyes of 61 participants) that had evaluated a topical medication instillation technique. We also identified two ongoing trials. Both included trials used a within-person design and administered prostaglandin monotherapy for glaucoma or ocular hypertension. Because the trials evaluated different instillation techniques and assessed different outcomes, we performed no meta-analysis.One trial, conducted in the US, evaluated the effect of eyelid closure (one and three minutes) versus no eyelid closure on lowering IOP. At one to two weeks' follow-up, reduction in IOP was similar in the eyelid closure group and the no eyelid closure group (mean difference (MD) -0.33 mmHg, 95% confidence interval (CI) -0.8 to 1.5; 51 participants; moderate-certainty evidence).The second trial, conducted in Italy, evaluated the effect of using an absorbent cloth to wipe excess fluid after instillation (fluid removal) versus not using an absorbent cloth (no removal) on reducing dermatologic adverse events. At four months' follow-up, eyelashes were shorter among eyes in the fluid removal group compared with the no fluid removal group (MD -1.70 mm, 95% CI -3.46 to 0.06; 10 participants; low-certainty evidence). Fewer eyes showed skin hyperpigmentation in the eyelid region towards the nose in the fluid removal group compared with the no removal group (RR 0.07, 95% CI 0.01 to 0.84; 10 participants; low-certainty evidence); however, the difference was uncertain in the eyelid region towards the temples (RR 0.44, 95% CI 0.07 to 2.66; 10 participants; low-certainty evidence). The effect hypertrichosis (excessive hair growth) was uncertain between groups (RR 1.00, 95% CI 0.17 to 5.98; 10 participants; low-certainty evidence).Neither trial reported other outcomes specified for this review, including the proportion of participants with IOP less than 21 mmHg; participant-reported outcomes related to the ease, convenience, and comfort of instillation techniques; physiologic measurements of systemic absorption; escalation of therapy; mean change in visual fields; optic nerve progression; mean change in best-corrected visual acuity; proportion in whom glaucoma developed; quality of life outcomes; or cost-effectiveness outcomes. Neither trial reported data at follow-up times of more than four months. Evidence to evaluate the effectiveness of topical medication instillation techniques for treatment of glaucoma is lacking. It is unclear what, if any, effects instillation techniques have on topical medical therapy for glaucoma.

Management lacrimal sac abscesses using lacrimal probe and crawford silicon tube.

BackgroundTreatment of lacrimal sac abscess of the traditional surgical approach may result in complications from cutaneous fistula formation, damage the sac, cause skin scarring and even have the potential for inducing cicatricial ectropion. We designed a new treatment scheme that is expected to achieve internal drainage with the use of lacrimal probe and crawford silicon tube.MethodsA prospective study was performed for the management of lacrimal sac abscesses. All suitable patients from January 2011 to June 2014 were managed by lacrimal probe and crawford tube insertion. Postoperatively, patients received 0.5% Levofloxacin eye drops four times per day and oral Levofloxacin tablets 0.5 g once per day for four days. Follow-up times were for more than three months after removing the Crawford tube. The condition of the lacrimal sac and the patient’s symptoms were carefully evaluated.ResultsFourteen patients suffering from lacrimal sac abscesses were included in this study. A history of chronic dacryocystitis was found in six patients, after acute dacryocystitis was found in three patients, and nasolacrimal occlusion with epiphora was found in other five patients. Resolution of signs and symptoms of lacrimal sac abscesses in all fourteen patients. No recurrence of lacrimal sac abscesses occurred during the median follow up period of 20.9 ± 7.8 months (range 6–36 months). Epiphora reoccurred in four patients.ConclusionsLacrimal probe and crawford silicon tube is successful as a procedure of choice for lacrimal sac abscesses. The insertion of a Crawford tube also offers potential advantages over standard treatment with the lack of recurrence of dacryocystitis or infection in post-surgical patients.

Blind recognition of mixed and disturbed correlated ancient texts

This study aims to evaluate the safety and effectiveness of a new approach to locate lacrimal sac using nasal endoscopy guided by intra-lacrimal duct fiber optics during nasolacrimal ostomy. 31 patients with recurrent dacryocystitis were chosen for nasolacrimal ostomy using nasal endoscope. During the surgery, fiber optic was inserted into lacrimal duct to project the light through the lacrimal sac, subsequently creating a light spot on the lateral wall of the nasal cavity to guide the process of locating lacrimal sac. Using this approach, we were able to rapidly and precisely locate lacrimal sac in all patients, leading to a simplified and significant shortened nasolacrimal ostomy surgical procedure. Nasolacrimal occlusion occurred in two patients, while all other patients were cured (overall success rate 93.55%) with no complication or recurrence within the 2 years post-procedure follow-up. The study thus revealed that intra-lacrimalduct fiber optic guidance is a feasible, safe and effective way to locate lacrimal sac during the lacrimal ostomy. Key words: Intra-lacrimal duct fiber optics, lacrimal sac, fiber optic-guided surgery, positioning.

Proposed Mandate for Instructions and Labeling Regarding the Use of Eye Drops

The potential clinical benefits of nasolacrimal occlusion (NLO) and eyelid closure (ELC) for 5 minutes have been recognized for many years. 1.9 Following the ocular instillation of drugs prepared in solutions, suspensions, and ointments, the pharmacologically active chemicals within these vehicles are pumped from the periocular area by the eyelids down the nasolacrimal outflow paths to the nasal mucosa. 10 This results in less intraocular drug absorption. In addition, the vascular nasal mucosa can readily absorb the drugs delivered in these vehicles, resulting in measurable systemic blood levels, which can be associated with significant systemic toxicity. 11 Therefore, the rapid passage of eye drops into the nasolacrimal outflow system effectively minimizes therapeutic effect and maximizes systemic toxicity of topically applied medications. 1 .

Congenital nasolacrimal duct occlusion with clinical anophthalmos: a possible new association

Purpose: To report the association of congenital nasolacrimal duct occlusion and clinical anophthalmos in an eight-year-old girl. Methods: A case report. The patient suffered from epiphora and clinical anophthalmos on the right side since birth. This paper presents the clinical presentation, workup, and surgical approach of the case. Results: The nasolacrimal system of the patient was occluded on irrigation. Computed tomography showed a blockage at the level of the sac-duct junction, an enlarged nasolacrimal duct below the obstruction, and a sclera-like ball of tissue surrounded by extraocular muscles in the right orbit. Treatment included a right bicanalicular silicon intubation performed under general anesthesia. Conclusion: This case may represent a new association that has not been previously reported.

シタラビン大量療法時の眼障害回避に対するステロイド点眼液の適正使用の効果

Although the use of corticosteroid (CS) eye drops of the use of eye washing by artificial tears was effective for the prevention of ocular toxicity such as keratitis and photophobia in the high-dose cytosine arabinoside (Ara-C) therapy, the toxicity was not prevented perfectly. We studied the effects of the rational use of CS eye drops, and the combined use of CS eye drops and eye washing by physiological saline in order to prevent the ocular toxicity. Before the study, the instillation of 0.1% sodium bethamethazone phosphate (BM) eye drops was carried out at 4-6 times per day during the high-dose Ara-C therapy, and continued for several days after the high-dose Ara-C therapy. However, the rational use of "eyelid closure" and "naso-lacrimal occlusion" after the instillation was not performed Consequently, the ocular toxicity was observed in 3 (19%) of 16 cases of the patients. When the instillation of BM eye drops at 4 times per day was carried out rationally according to the consultation of pharmacist during the high-dose Ara-C therapy and for additional 10 days after the therapy, no ocular toxicity was observed in all cases (0 of 6 cases). Furthermore, the combined use of eye washing by physiological saline and instillation of BM eye drops was effective for the decrease of the risk of ocular toxicity, because no ocular toxicity was observed in the high-dose Ara-C therapy (0 of 34 cases). Our procedure in this study would be effective for the prevention of ocular toxicity in the high-dose Ara-C therapy.

医薬品の適正使用とその実践 ＶＩ． β‐遮断薬含有点眼剤の適正使用のための服薬指導とその評価，および相互作用・副作用の回避法

This study examined the actual condition on the use of beta-blocker eye drops, and the duplicated prescription of eye drops. Patients were thus surveyed on the rational use of beta-blocker eye drops carried out through personal interviews at our Pharmacy Department counter. The results showed that the practice rate of the “instillation of one drop of the eye drops” was 55 (78%) of 71 patients, while “eyelid closure for 1 minute after application” was 45%, and “nasolacrimal occlusion for 1 minute after application” was observed in 20%. The practice rates of “eyelid closure” and “nasolacrimal occlusion” were increased about 2 fold, respectively, as compared with the data obtained one year earlier. This may be due to the abouve extra consultation. However, these practice rates were still small. This indicates that many patients may be not fully aware of the importance of such practice. Therefore, further education will be needed to instruct patients in the rational use of the eye drops.The results of prescription surveys in 6500 sheets for 3 months from November, 1995 to January, 1996 showed that the total number of over-prescription of beta-blocker eye drops and calcium antagonist internal medicine was found to be 105. These results show that we must constantly check for duplicated prescription to patients prescribed beta-blocker eye drops, while furthermore, comprehensive provision of drug information on the development and prevention of the systemic side effects of beta-blocker eye drops to oculists and physicians is also essential.

Treatment of complete and partial obstruction of the nasolacrimal system with polyurethane stents: initial experience.

To present our experience in the treatment of nasolacrimal occlusion by means of polyurethane stents. Forty polyurethane stents were placed under fluoroscopic guidance in 35 consecutive patients with epiphora due to total or partial obstruction of the nasolacrimal system. The set designed by Song was used in all patients. The procedure was performed by introducing a guidewire through the superior punctum into the canaliculus and advancing it across the obstruction into the inferior meatus of the nasal cavity. After pulling out the guidewire, the stent was advanced in retrograde fashion and released into the sac and the nasolacrimal duct. The technical success rate was 100%. The average time for the procedure was 25 min (range 10-60 min). Immediate complications were: mild pain (n = 5), severe pain (n = 1), minimal epistaxis (n = 7), and moderate epistaxis (n = 1). No major complications occurred. The last clinical control revealed complete resolution of epiphora in 35 eyes and partial resolution in four; one patient did not improve. This technique for treatment of obstruction of the nasolacrimal system is simple and safe, and may obviate the use of more invasive procedures.

Effects of Ocular Betaxolol on Glucose and Lipid Metabolism after Long-Term Treatment

Seventy-five healthy adult men with ocular hypertension or recently diagnosed primary open angle glaucoma were enrolled in a prospective, randomised, double-blind study to determine the effects of an ocular β1-selective antagonist, betaxolol 0.5%, on plasma total cholesterol, high density fraction, triglycerides and glucose during a treatment period of 6 months. Group A, consisting of 40 patients, received 0.5% betaxolol 1 drop in both eyes twice daily without nasolacrimal occlusion; group B, involving 35 patients, received only the vehicle of betaxolol (placebo), in the same doses without nasolacrimal occlusion. Cardiac parameters such as atrioventricular conduction, pulse rate and both systolic and diastolic blood pressure were controlled during the study. After monthly checks and at the end of the trial, betaxolol did not produce any significant variations in plasma lipid and glucose levels in the patients examined. To the best of our knowledge, this is the first study to evaluate the effects of a β1-selective β-blocker for ocular use on lipid and glucose metabolism over a prolonged treatment period.

医薬品の適正使用とその実践 Ｖ； 点眼液の服薬指導の効果と指導方法の評価

We studied the effect of advising outpatients on the rational use of ophthalmic solutions and compliance by a questionnaire (n=158), in order to establish the optimal consultation method. A total of 41.8% of the patients answered the questionnaire. In compairing the actual use of ophthalmic solutions before and after consultation, the rates of rational use increased for all items except for “applications per day”, which decreased slightly from 93.4% before the consultation to 90.2% after that. In particular, “eyelid closure” and “nasolacrimal occlusion” after instillation, and “the 5 min interval of instillation in the case of plural medication”, considerably increased from 34.8% before the consultation to 60.6% after that, from 9.5% to 50.8% and from 45.9% to 73.8%, respectively. The compliance remarkably improved in glaucoma patients after consultation regarding “the 5min interval of instillation” .Based on these results, our consultation method for the rational use on ophthalmic solutions was thus evaluated. However, since some patients who still did not appreciate the need for the rational use of such medication still presented, further improvements in the consultation method requires for the rational use.

The effect of nasolacrimal occlusion on drug-induced mydriasis

Nasolacrimal occlusion has been shown to improve the efficacy of some topically applied ocular drugs. The aim of this study was to investigate the effect of nasolacrimal occlusion on tropicamide-induced mydriasis. We compared pupillary dilatation by 0.125% tropicamide with and without nasolacrimal occlusion in 40 healthy volunteers. Analysis of variance with repeated measures failed to show any advantage due to nasolacrimal occlusion in drug-induced mydriasis. Nasolacrimal occlusion did not increase the mydriasis obtained with 0.125% tropicamide.

Perspectives in the drug treatment of glaucoma

Pharmacological hypotensive therapy has been a mainstay of glaucoma treatment. Recently, several new families of medications have been discovered. These compounds not only reduce intraocular pressure but may produce an additive effect when combined with conventional glaucoma medications. Thus in the near future, the clinician will have an “arsenal” of medications available to achieve a patient's selected target intraocular pressure. The technique of nasolacrimal occlusion may be increasingly important in the minimization of systemic effects. This review provides a selective summary of the new families of pharmacologic agents and their potential use with conventional glaucoma medications. In addition, recent advances in (3-blockers, new indications for the use of apraclonidine, choices of pharmacologic agents used after surgery, and the treatment modalities of normal-tension glaucoma are reviewed.

Effects of Ocular Carteolol and Timolol on Plasma High-density Lipoprotein Cholesterol Level

Fifty-eight healthy, normolipidemic adult men participated in a prospective, masked, randomized crossover study designed to compare the effects of two topical nonselective beta-adrenergic antagonists, carteolol and timolol, on plasma high-density lipoprotein cholesterol levels. Two eight-week treatment periods were separated by an eight-week drug-free period. Carteolol 1.0% or timolol 0.5% was used, one drop twice daily, in both eyes without nasolacrimal occlusion. Fresh plasma was assayed for levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and apolipoproteins A-I and B-100. With indistinguishable effects on intraocular pressure, carteolol and timolol induced different (P = .013) decrements in high-density lipoprotein cholesterol levels. Carteolol treatment decreased high-density lipoprotein cholesterol levels by 3.3% (-0.04 mmol/l) and raised the ratio of total to high-density lipoprotein cholesterol levels by 4.0% (0.15 unit); timolol treatment decreased high-density lipoprotein cholesterol levels by 8.0% (-0.10 mmol/l) and raised the ratio of total to high-density lipoprotein cholesterol levels by 10.0% (0.37 unit). There was no differential drug effect on the other lipid variables measured. Ocular nonselective beta-adrenergic antagonist therapy can produce clinically relevant decrements in high-density lipoprotein cholesterol levels in healthy men.

Systemic Absorption Pathways of Topically Applied Beta Adrenergic Antagonists in the Pigmented Rabbit

The objective of this study was to determine the influence of drug lipophilicity on extent of systemic absorption and relative contributions of the nasal and conjunctival mucosae to systemic absorption following topical solution instillation in the pigmented rabbit. Relatively hydrophilic atenolol, moderately lipophilic timolol and levobunolol, and lipophilic betaxolol were chosen as model drugs. Twenty-five microliters of a 15 mM drug solution in isotonic pH 7·4 buffer was instilled in each eye, with or without nasolacrimal occlusion, and plasma drug concentration was monitored using reversed phase HPLC. An equivalent amount of all four β adrenergic antagonists was instilled directly into the nasolacrimal duct to assess the nasal contribution to systemic drug absorption following topical solution instillation. The systemic bioavailability ranged from 61% for atenolol to 100% for timolol. At least 50% of the systemically absorbed drug reached the bloodstream from the nasal mucosa: the nasal contribution was 83% for atenolol and 55-74% for the other three drugs. Occluding the nasolacrimal duct for 5 min reduced the extent of systemic absorption of timolol and levobunolol but did not do so for atenolol and betaxolol. Additional prolongation of solution retention in the conjunctival sac brought about further reduction for only atenolol (480-min prolongation) and timolol (120-min prolongation). Taken together, the above findings suggest that the systemic bioavailability of topically applied ophthalmic drugs would be modest for drugs at the extremes of lipophilicity and that the contribution of the nasal pathway to systemically absorbed drug diminishes with increasing drug lipophilicity.