New application of an old drug proparacaine in treating epilepsy via liposomal hydrogel formulation.

Proparacaine (PPC) is a previously discovered topical anesthetic for ophthalmic optometry and surgery by blocking the central Nav1.3. In this study, we found that proparacaine hydrochloride (PPC-HCl) exerted an acute robust antiepileptic effect in pilocarpine-induced epilepsy mice. More importantly, chronic treatment with PPC-HCl totally terminated spontaneous recurrent seizure occurrence without significant toxicity. Chronic treatment with PPC-HCl did not cause obvious cytotoxicity, neuropsychiatric adverse effects, hepatotoxicity, cardiotoxicity, and even genotoxicity that evaluated by whole genome-scale transcriptomic analyses. Only when in a high dose (50 mg/kg), the QRS interval measured by electrocardiography was slightly prolonged, which was similar to the impact of levetiracetam. Nevertheless, to overcome this potential issue, we adopt a liposome encapsulation strategy that could alleviate cardiotoxicity and prepared a type of hydrogel containing PPC-HCl for sustained release. Implantation of thermosensitive chitosan-based hydrogel containing liposomal PPC-HCl into the subcutaneous tissue exerted immediate and long-lasting remission from spontaneous recurrent seizure in epileptic mice without affecting QRS interval. Therefore, this new liposomal hydrogel formulation of proparacaine could be developed as a transdermal patch for treating epilepsy, avoiding the severe toxicity after chronic treatment with current antiepileptic drugs in clinic.

Comparison of Topical Versus Peribulbar Anesthesia for 23G Pars Plana Vitrectomy.

OBJECTIVE: To compare the safety and efficacy of topical anesthesia versus peribulbar anesthesia for 23-gauge pars plana vitrectomy. STUDY DESIGN: Randomized controlled trial. PLACE AND DURATION OF STUDY: Ophthalmology Department, Lahore General Hospital, Ameer-ud-Din Medical College, Postgraduate Medical Institute, Lahore from April 2013 to March 2016. METHODOLOGY: A total of 110 patients were equally divided (n=55) in group A (topical anesthesia) and group B (peribulbar anesthesia). In group A, pledget soaked with 0.5% proparacaine hydrochloride were placed in the superior and inferior fornices three minutes before surgery, and removed just before surgery. For group B patients, 3 ml of 0.5% bupivacaine was used for peribulbar anesthesia three minutes before surgery. Surgical time was noted from the placement of pledget in fornix till the eye pad placed in group A, and from the time of peribulbar anesthesia in group B till the eye pad placed at the end of surgery. All data was recorded in Excel sheet and p-values were calculated using online OpenEpi. RESULTS: The mean age of the patient was 56.28 ±13.76 years. Male patients were 78 (70.9%) and female patients were 32 (29.1%). Mean duration of surgery was 30.32 ±7.07 minutes and mean pain score was 2.30 ±0.98. There was a significant difference with respect to mean duration of surgery in patients who were given topical anesthesia (32.52 ±6.92 minutes) versus those given peribulbar anesthesia (28.12 ±6.57 minutes, p<0.001). Mean pain score in topical anesthesia group (3.11 ±0.89) was significantly higher as compared to peribulbar anesthesia group (2.67 ±0.91, p=0.011). CONCLUSION: Topical anesthesia is as effective as peribulbar anesthesia in terms of patient comfort and duration of surgery for 23-G pars plana vitrectomy in patients with vitreous hemorrhage.

The Safety of Topical Anesthetics in the Treatment of Corneal Abrasions: A Review.

BACKGROUND: Despite the fact that topical anesthetics provide superb analgesia to the painful eye, they are not prescribed routinely to patients when they are discharged from the emergency department because of concerns for delayed healing and corneal erosion. OBJECTIVE: To summarize the evidence for the safety of topical proparacaine and tetracaine for pain relief in patients with corneal abrasions. METHODS: This is a systematic review looking at the use of topical anesthetic agents in the treatment of corneal abrasions in the emergency department. RESULTS: Our literature search produced two emergency department-based, randomized, double blind, placebo-controlled studies on human patients with corneal abrasions. Additionally, we found four studies that investigated the application of topical anesthetics in patients who underwent photorefractive keratectomy. All six studies demonstrated that a short course of dilute topical anesthetic provided efficacious analgesia without adverse effects or delayed epithelial healing. CONCLUSION: Limited available data suggests that the use of dilute topical ophthalmologic proparacaine or tetracaine for a short duration of time is effective, though their safety for outpatient use is inconclusive.

Topical proparacaine abuse resulting in evisceration.

A 72-year-old man was admitted to our clinic because of pain in the right eye. Corneal oedema, peripheral anterior synechiae formation and intraocular lens were determined in the right eye. The left eye was normal except for nuclear sclerosis. Intraocular pressure was 35 mm Hg in the right eye and 14 mm Hg in the left eye. The patient was diagnosed as having bullous keratopathy and glaucoma. He was treated with antiglaucoma drugs and artificial tears as an outpatient. Persistent keratopathy was observed at follow-up, despite adequate therapy. In the detailed anamnesis of the patient, we discovered that he had used a topical anaesthetic instead of the prescribed medicine owing to ocular pain. The patient was still using topical anaesthetic eye drops, despite warnings. Finally, evisceration was performed on his right eye because of corneal melting and perforation.

Combined topical and intracameral anesthesia for Descemet's stripping automated endothelial keratoplasty.

To evaluate the use of combined topical and intracameral anesthesia for Descemet's stripping automated keratoplasty (DSAEK). This was a retrospective comparative cohort analysis consisting of 10 eyes in 10 consecutive patients undergoing DSAEK surgery with combined topical and intracameral anesthesia. These cases were compared with 21 randomly selected controls during the same time period undergoing DSAEK surgery performed under retrobulbar anesthesia. Incidence of intraoperative and postoperative complications, and endothelial cell counts were compared. In all cases, DSAEK was completed without intraoperative complications. All patients tolerated the procedure well. There were 6 cases of postoperative graft dislocation requiring rebubbling, and no cases of primary failure or endophthalmitis. No significant difference in endothelial cell counts was found at final follow-up. Short-term results suggest that combined topical and intracameral anesthesia is as safe and effective for DSAEK in cooperative patients when compared to retrobulbar anesthesia. It may thereby be an alternative anesthetic modality for patients in whom retrobulbar or peribulbar anesthesia may be risky or contraindicated.

Topical anesthetic abuse keratopathy: a commonly overlooked health care problem.

PURPOSE: To evaluate the clinical course, treatment modality, factors affecting the epithelization period, and visual outcome in patients with topical anesthetic abuse keratopathy. METHODS: The medical records of 19 patients with a confirmed diagnosis of topical anesthetic abuse keratopathy were retrospectively examined; occupation, initiating event, biomicroscopic findings, treatment modality, epithelization period, and best-corrected visual acuity (BCVA) were noted. The Wilcoxon signed rank test was used to compare BCVA before and after treatment; P values <0.05 were considered statistically significant. RESULTS: In all, 26 eyes in 19 men aged 21-44 (mean age: 31 ± 6) years were included. Initiating events included exposure to arc welding flash (8 patients), metallic foreign body injury (8 patients), and chemical injury (3 patients). On admission to hospital, 10 patients (52.6%) reported that they were using topical anesthetics. Upon admission to the hospital, 10 patients (52.6%) self reported that they were using topical anesthetics. The remaining 9 subjects were discovered to be using topical anaesthetic drops during hospitalization. Twelve patients (63.2%) were found to continue using these agents during their hospitalization. Oval corneal epithelial defect, stromal infiltrate, ring-shaped keratitis, and hypopyon were noted in 100%, 46.2%, 57.7%, and 42.3% of the eyes, respectively. Topical antibiotics (fluoroquinolones or combined fortified cephalosporins and aminoglycosides), preservative-free lubricants/autologous serum, and bandage contact lens/eye patches were used for treatment. Mean epithelization period was 19.96 ± 11.16 days (range: 6-50 days). Mean pretreatment and posttreatment BCVA was 0.12 ± 0.16 (range: 0.001-0.7) and 0.66 ± 0.30 (range: 0.0-1.0), respectively (P < 0.001). CONCLUSIONS: Ophthalmologists should be suspicious of topical anesthetic abuse keratopathy in young male manual laborers specialized in welding business and foundry work presenting with persistent epithelial defects, ring-shaped keratitis, and accompanying severe ocular pain.

Effect of a proparacaine 0.50%-sodium fluorescein 0.25% mix and contact ultrasound pachymetry on central and midperipheral corneal thickness measured by noncontact optical pachymetry.

PURPOSE: To assess the effect of a combination of proparacaine 0.50%-sodium fluorescein 0.25% and ultrasound (US) pachymetry on central and midperipheral corneal thickness. SETTING: School of Optometry and Vision Sciences, Cardiff University, Cardiff, Wales, United Kingdom. DESIGN: Case series. METHOD: Topographic measurements of corneal thickness in healthy right eyes were obtained using a scanning-slit device (Orbscan IIz) and a Scheimpflug device (Pentacam) before and after application of proparacaine 0.50%-sodium fluorescein 0.25% and US pachymetry. Changes in corneal thickness in the center and 2.5 mm from the center in the temporal, nasal, inferior, and superior locations were assessed. RESULTS: The study evaluated 35 eyes. The scanning-slit and Scheimpflug devices recorded a small but statistically significant increase in corneal thickness at all locations (mean 4.9 ± 14.3 [SD] to 9.1 ± 11.7 µm; P<.05, paired t test). The cornea swelled uniformly across its diameter (scanning slit, P=.934; Scheimpflug, P=.654; analysis of variance); there was no statistically significant difference in the amount of swelling between the 2 devices (P>.05, t test). The 95% limits of agreement were broad (-10 to +30 µm), suggesting a large degree of interindividual variability. CONCLUSIONS: Ultrasound pachymetry combined with proparacaine 0.50%-sodium fluorescein 0.25% caused a small (<10 µm) but significant amount of corneal swelling on average. Because the effect on corneal thickness may be greater than -10 to +30 µm in individual cases, clinicians should avoid contact procedures before obtaining topographic maps of corneal thickness using scanning-slit and Scheimpflug devices.

Ring keratitis associated with topical abuse of a dilute anesthetic after refractive surgery.

Anesthetic toxic keratitis is rare and presents as a ring keratitis, which is often misdiagnosed as Acanthamoeba keratitis. Here, we report an unusual case of toxic keratitis caused by topical abuse of a dilute anesthetic. A 26-year-old woman presented with bilateral corneal edema, ring infiltrates, pigmented keratic precipitate, Descemets membrane folding, and strong anterior chamber reactions 2 weeks after laser subepithelial keratomileusis surgery. Tracing back her medical history, topical dilute 0.1% proparacaine was prescribed and frequently used for 1 month. Toxic keratitis was suspected. After discontinuation of the topical anesthetic and initiation of treatment with topical 20% autologous serum, complete corneal epithelialization was achieved within 1 week. Corneal infiltrates and anterior chamber reaction gradually subsided. Vision improved from finger counting to 20/20 in the right eye and 20/25 in the left eye, but confocal microscopy showed decreased corneal endothelial cells. Topical abuse of a dilute topical anesthetic can cause severe toxic keratitis and endothelial cell loss. The physician must be aware of the signs of topical anesthetic abuse and should not prescribe even a dilute anesthetic for long-term use. Autologous serum can help in the recovery of toxic keratitis.

An atypical presentation of acanthamoeba keratitis in a patient with keratoconus treated briefly with topical anesthetic.

OBJECTIVES: To present a case of biopsy proven acanthamoeba keratitis requiring penetrating keratoplasty in a patient with keratoconus whose clinical course was remarkable for its lack of ocular injection and pain. The absence of these key findings may have contributed to a delay in diagnosis and a delay in instituting antiamoebic therapy. METHODS: Case report. RESULTS: A 21-year-old woman who wore soft contact lenses for management of keratoconus presented with a painful suppurative corneal infiltrate and epithelial defect. The patient was initially seen in an emergency department where she was given a bottle of topical anesthetic drops (proparacaine) to use for pain. When she was seen by the authors 18 hr after presenting to the emergency department, the proparacaine was immediately discontinued, and she was treated with fortified antibiotic (vancomycin and tobramycin) eye drops and oral antiviral medications (famciclovir). Despite an initial improvement and complete resolution of ocular discomfort, the patient went on to develop a dense, peripheral stromal infiltrate that failed to improve despite intensive treatment. Confocal microscopy and corneal biopsy were definitive for acanthamoeba infection. The patient subsequently failed medical therapy and underwent large diameter penetrating keratoplasty. The patient has shown no evidence of acanthamoeba recurrence in the corneal graft. CONCLUSIONS: Keratoconic patients may have atypical presentations of acanthamoeba keratitis, which may delay diagnosis and institution of medical therapy. Even brief use of topical anesthetics may further complicate the clinical picture.

[Self-medication with local anaesthetics by glaucoma patients using teletonometry]. / Selbstmedikation mit Lokalanästhetika durch Glaukompatienten bei der Teletonometrie.

BACKGROUND: Self-tonometry, a supplementary measurement of the intraocular pressure in ophthalmology by glaucoma patients using an automatic tonometer, will become more and more important in the future. As long as the self-tonometry has to work in the contact modus with the ocular surface, home application of a topical anaesthetic by the glaucoma patient will be a requirement for a successful measurement. So far no severe problems within this controlled self-medication have been seen. Nevertheless, public health authorities believe patient health is put at high risk by the application of local anaesthetics during self-tonometry. As there are no clinical studies of the health care, we evaluated the local tolerability of a topical anaesthetic in line with self-tonometry employing a modified tonometer OCUTON S. MATERIAL AND METHODS: A total of 100 glaucoma patients participated in a prospective clinical study of the routine clinical service in which each was monitored for 1 year. The telemonitoring involved self-tonometry for at least 6 months in every case and Ocuton S Proparakain-POS 0.5% eyedrops (proxymetacaine-HCl) were applied by the probands before every measurement of the intraocular pressure with a modified self-tonometer. Information regarding the local tolerability of the topical anaesthetic was analysed using a standardised questionnaire. The intensity of the following subjective symptoms was listed in separate visual analogue scales for: lacrimation, burning, foreign body sensation, mucus aggregation, pruritus and pain. RESULTS: Information from 83 glaucoma patients on local tolerability of proparacaine eyedrops could be analysed. For several reasons no data could be gathered from 17 probands, which were refusal to complete the questionnaire, cancelled participation and, in two test persons, there emerged an allergic reaction (local eyelid redness and swelling) which necessitated a change to a different topical anaesthetic. In all other participants the application was carried out without any significant local or systemic symptoms or side-effects. Immediately after application of the eyedrops 36.1% of the test persons suffered a minor conjunctival hyperaemia which eased off within 1 h in 20.4% of these patients. Of the interviewed glaucoma patients 91.5% judged the single symptoms on the visual analogue scale between zero and medium intensity. The severest effects, according to the subjective evaluation, were felt in symptoms of burning with a score of 94 and lacrimation graded 96. The least intensity was established in the symptom of mucus aggregation where 72.3% rated this symptom in the visual analogue scale between 0 and 10. The other symptoms pruritus, feeling of pressure and foreign body sensation hardly differed in subjective ratings. CONCLUSION: A self-medication with topical anaesthetics on undamaged ocular surfaces for self-tonometry purposes can be performed by glaucoma patients without a high risk potential. However, the application presupposes that routine ophthalmological examinations are carried out according to the ophthalmological associations' recommendations. Therefore, medical care concepts which integrate self-tonometry into routine ophthalmological services and comply with the complex requirements of a modern glaucoma management should be applied more often.

An assessment of the discomfort associated with the use of rose bengal 1% eyedrops on the normal human eye: a comparison with saline 0.9% and a topical ocular anaesthetic.

PURPOSE: To assess the time-dependent changes in ocular comfort following unilateral instillation of preservative-free rose bengal 1% eyedrops when compared with saline 0.9% or proxymetacaine 0.5%. METHODS: A total of 61 subjects, aged between 19 and 77 years, were asked to complete an ocular symptoms questionnaire, and then to indicate the comfort level for each eye on a 100-point visual analogue scale (VAS). A single drop of rose bengal was instilled in one eye (left or right) and a drop of saline or anaesthetic instilled in the other eye. The VAS assessments were repeated at an average of 4 and 7 min later. RESULTS: The instillation of rose bengal eyedrops produced an initial average reduction in comfort of 39.8 points, as compared with a reduction of 11.5 points following the anaesthetic and a reduction of 3.4 points for saline. However, the responses to rose bengal were highly variable, ranging from reductions of 1.5 to 84.6 points. In most subjects, some recovery had occurred within 6-8 min, but the comfort scores averaged 27.8 points below baseline levels prior to rose bengal. Slightly greater discomfort was noted by older subjects and those with darker irides. CONCLUSIONS: This study confirms that the use of rose bengal eyedrops can elicit a sensation of discomfort, but that this adverse reaction does not last very long. Based on the initial kinetics of recovery from discomfort, it is estimated that this should last no longer than 10-15 min (at least for those without significant ocular surface disease).

Anaesthetic abuse keratopathy as a manifestation of ocular Munchausen's syndrome.

Two patients, both with a history of major depressive disorder, presented with large bilateral corneal epithelial defects and ring-shaped stromal opacities. Both were initially treated unsuccessfully with topical antibiotic therapy for presumed infectious keratitis. One patient eventually admitted to topical anaesthetic abuse. In the second patient, signs of topical anaesthetic abuse and Munchausen's syndrome became evident. Cessation of anaesthetic use resulted in rapid resolution of the corneal epithelial defects in both patients. Anaesthetic abuse keratopathy is often a manifestation of underlying psychiatric illness, and psychiatric intervention is a very important part of management. To the authors' knowledge, this is the first report of ocular Munchausen's syndrome manifesting as anaesthetic abuse keratopathy.

Subtenon lidocaine vs topical proparacaine in adult strabismus surgery.

Intraoperative subtenon 2% lidocaine and topical 0.5% proparacaine in patients undergoing strabismus surgery were compared. No additional systemic analgesics and sedatives were used. Mean and total pain scores intraoperatively and postoperatively were not different. Each anesthetic agent provides good intraoperative anesthesia and postoperative analgesia. Topical 0.5% proparacaine may be preferred because of its easy administration and fewer side effects, lack of hospital admission, and immediate and predictable alignment of the eyes.

Allergic contact dermatitis to proparacaine with subsequent cross-sensitization to tetracaine from ophthalmic preparations.

We report 2 cases of allergic contact dermatitis (ACD) to proparacaine and tetracaine. Patient 1 is an ophthalmologist with chronic finger pad dermatitis sensitized to the topical anesthetic proparacaine. Despite discontinuance of proparacaine and substitution with a patch test negative agent, tetracaine, his hand dermatitis persisted. Follow up patch testing documented that acquisition of contact allergy to tetracaine as well as thiuram had taken place. Patient 2 had a periocular eczematous dermatitis with ACD to both proparacaine and tetracaine. Cross sensitization between related topical ophthalmologic anesthetics has been suggested to be a rare occurrence. We suggest that allergic sensitization and possible cross-reaction to topical anesthetics in ophthalmologists and ophthalmologic technicians is an occupational hazard. Chronically eczematized skin might result in increased exposure to contact allergens and result in concomitant allergic sensitization. ACD to topical anesthetic agents among ophthalmologists should be recognized as a potential hazard.

A comparison of Fluoracaine and Fluorox on corneal epithelial cell desquamation after Goldmann Applanation Tonometry.

BACKGROUND: The purpose of this study was to quality the frequency and amount of corneal desquamation from a sodium fluorescein/proparacaine combination (Fluoracaine) as compared with sodium fluorescein/benoxinate combination ophthalmic solution (Fluorox) after Goldmann Applanation Tonometry. METHODS: One drop of Fluoracaine was randomly instilled into one eye and one drop of Fluorox was instilled into the opposite eye of the same patient. Intraocular pressures (IOPs) by GAT and tear break-up times (TBUTs) were taken. Corneal stinging was compared. Corneal integrity by Cornea and Contact Lens Research Unit (CCLRU) standards was evaluated at 0, 3, 7, 10, 15, and 20 minutes after instillation of the ophthalmic solutions. RESULTS: Sixty eyes of 30 patients were observed Forty-seven percent of the patients reported Fluorox to string more than Fluoracaine; 23% of the patients reported that Fluoracaine stings more than Fluorox; and 30% the patients reported no difference. Average TBUTs were 6.87 and 7.17 seconds with Fluoracaine and Fluorox, respectively. Fluoracaine produced micro- and macropunctate keratitis of the superficial epithelium in 31% to 45% of the cornea. Fluorox caused superficial micropunctate keratitis in about 16% to 30% of the cornea. At 20 minutes, all eyes with Fluoracaine and all eyes but one with Fluorox had corneal desquamation. CONCLUSIONS: Fluoracaine causes marginally less stinging--however, clinically and statistically more corneal desquamation--than Fluorox after GAT. Corneal integrity after use of Fluoracaine should be evaluated even 20 minutes after GAT procedures for corneal disruption.

Fingertip dermatitis in an ophthalmologist caused by proparacaine.

PURPOSE: To report the late diagnosis of allergic response to proparacaine hydrochloride in an ophthalmologist. METHOD: Case report. In a 49-year-old practicing ophthalmologist, the history, clinical findings of fingertip dermatitis, skin pathology, and skin patch testing are described. RESULTS: Proparacaine, as the initiating agent, took almost 3 years to identify because of the unusual pattern of allergy. We explored numerous treatment options before identifying and removing the offending agent. CONCLUSIONS: Ophthalmologists may be exposed to proparacaine on a daily basis. This unique report heightens the awareness of this rare work-related complication.

Topical anesthetic abuse after radial keratotomy.

A 49-year-old woman developed corneal epithelial defects and stromal infiltration shortly after a 4-cut radial keratotomy (RK) for myopia. Although cultures grew staphylococci and appropriate antibiotic treatment was applied, the epithelial defects increased in size. The corneal epithelium did not heal fully for more than 2 months. Penetrating keratoplasty 1 year later was followed by epithelial breakdown and perforation, as was a second keratoplasty. Despite repeated questioning, the patient did not admit until 18 months after her initial surgery that she had begun self-treatment with dilute proparacaine shortly after RK and continued it after her keratoplasties. The elective use of topical anesthetics to control pain after refractive surgery should be approached with caution, and patients should be warned of the possible consequences of their misuse.

Topical diclofenac sodium in the management of anesthetic abuse keratopathy.

PURPOSE: To report a case of anesthetic abuse keratopathy and to suggest the use of topical diclofenac sodium in the management of this disorder. METHOD: Narcotics and topical diclofenac were used to control pain in a patient who developed a corneal ulcer after abusing topical anesthetics. RESULT: After the institution of topical diclofenac, the patient reported substantial improvement in comfort and less reliance on narcotic agents for analgesia. CONCLUSION: We found topical diclofenac to be useful in controlling pain in this patient with anesthetic abuse keratopathy.

Topical anesthetic abuse ring keratitis: report of four cases.

PURPOSE: We present the clinicopathologic correlations of two case and two other clinical cases of topical anesthetic abuse keratopathy that were originally diagnosed as Acanthamoeba keratitis because of ring keratitis presentation and characteristic history. METHODS: Four patients who were referred to us with suspected Acanthamoeba keratitis are included. Each was initially treated for amoebic keratitis, by using established protocols, and only later was the true origin (topical anesthetic abuse) uncovered. The clinical and surgical histories, pathologic analysis of the corneal specimens, and follow-up of < or = 4 years are included. RESULTS: Our four cases show another cause for ring infiltration of the cornea. Two cases resulted in corneal transplantation and multiple other medical or surgical treatments in an attempt to restore vision but had poor outcomes of finger-counting vision. Two other cases responded to intensive medical treatments with return of useful vision. Evaluation of the surgical specimens revealed a previously unpublished finding of near total cell death within the corneal stroma. CONCLUSION: Topical anesthetic abuse resulting in sight-threatening keratitis may be seen as a masquerade syndrome in many cases. Because of the often poor outcome, we must be aware of this entity, prevent abuse, and be vigilant in our prohibition of topical anesthetic for any therapeutic use.