Optogenetic Inhibition of Nav1.8 Expressing Corneal Afferents Reduces Persistent Dry Eye Pain.

Purpose: The aim of the present study was to investigate the contribution of Nav1.8 expressing corneal afferent neurons to the presence of ongoing pain in lacrimal gland excision (LGE)-induced dry eye. Methods: The proton pump archaerhodopsin-3/eGFP (ArchT/eGFP) was conditionally expressed in corneal afferents using Nav1.8-cre mice. Dry eye was produced by unilateral LGE. Real time place preference was assessed using a three-chamber apparatus. A neutral, unlit center chamber was flanked by one illuminated with a control light and one illuminated with an ArchT activating light. For real-time preference, animals were placed in the neutral chamber and tracked over five 10-minute sessions, with the lights turned on during the second and fourth sessions. In other studies, movement was tracked over three 10-minute sessions (the lights turned on only during the second session), with animals tested once per day over the course of 4 days. A local anesthetic was used to examine the role of ongoing corneal afferent activity in producing place preference. Results: The corneal afferent nerves and trigeminal ganglion cell bodies showed a robust eGFP signal in Nav1.8-cre;ArchT/eGFP mice. After LGE, Nav1.8-cre;ArchT/eGFP mice demonstrated a preference for the ArchT activating light paired chamber. Preference was prevented with pre-application to the cornea of a local anesthetic. Nav1.8-cre;ArchT/eGFP mice with sham surgery and LGE wild-type control mice did not develop preference. Conclusions: Results indicate LGE-induced persistent, ongoing pain, driven by Nav1.8 expressing corneal afferents. Inhibition of these neurons represents a potential strategy for treating ongoing dry eye-induced pain.

Modulating Ocular Surface Pain Through Neurokinin-1 Receptor Blockade.

Purpose: The purpose of this study was to test the role of substance P (SP) and its receptor neurokinin 1 (NK1R) on ocular surface pain. Methods: Eight-week-old C57BL6/N (wild type [WT]) and B6.Cg-Tac1tm1Bbm/J (TAC1-KO) male mice were used. 5 M NaCl was topically applied on the cornea, followed by topical fosaprepitant 2, 10, and 50 mg/mL; 4 mg/mL oxybuprocaine chloride, or 0.1% diclofenac. Th eye wiping test was used to quantify ocular surface pain. SP content was quantified in the tear fluid and trigeminal ganglia (TG), and TAC1 mRNA was assessed in the cornea. Corneas were immunostained for ß3-tubulin and NK1R, or CD45, to quantify leukocyte infiltration. Results: TAC1-KO mice displayed a significant reduction of ocular pain (P < 0.001). Similarly, a single dose of 10 or 50 mg/mL fosaprepitant applied topically to WT mice reduced ocular pain as compared to vehicle (P < 0.001). Fosaprepitant 2 mg/mL, instead, induced corneal analgesia only when it was administered for 10 days, 6 times/day (P < 0.05). Diclofenac or oxybuprocaine reduced corneal nociception when compared to vehicle or fosaprepitant (P < 0.05). Fosaprepitant or oxybuprocaine groups showed lower SP content in tear secretions and TG (P < 0.05), and reduction in TAC1 mRNA (P < 0.05), and leukocyte infiltration (P < 0.05) in the cornea. Colocalization of NK1R and ß3-tubulin was detected in mouse corneas. Conclusions: Topical administration of the NK1R antagonist fosaprepitant effectively reduces ocular surface nociception by decreasing SP release in the tear fluid and TG, and corneal leukocyte infiltration. Fosaprepitant repurposing shows promise for the treatment of ocular pain.

Safety and efficacy of nepafenac punctal plug delivery system in controlling postoperative ocular pain and inflammation after cataract surgery.

PURPOSE: To evaluate the safety and efficacy of a nepafenac punctal plug delivery system (N-PPDS) after cataract surgery. SETTING: Three U.S. clinical sites. DESIGN: Prospective, multicenter, randomized (2:1), parallel-arm, double-masked, placebo-controlled, phase II pilot study. METHODS: Fifty-six subjects (aged older than 22 years) with expected postcataract correctable distance vision of 20/30 or better and lower puncta allowing dilation up to 1.0 mm received either the nepafenac (N-PPDS group; n = 38 eyes) or a placebo punctal plug delivery system (p-PPDS group; n = 18 eyes). All eyes underwent routine unilateral cataract surgery with intraocular lens implantation. The primary and secondary efficacy measures were postoperative ocular pain and inflammation, respectively. RESULTS: There were 38 patients in the experimental N-PPDS group and 18 patients in the control group. The N-PPDS group had a significantly higher percentage of pain-free patients than that in the p-PPDS group (22/32 [69%] vs 6/16 [38%] at 3 days, P = .038; and 24/36 [67%] vs 5/16 [31%] at 7 days, P = .018). A higher percentage of patients in the N-PPDS group (15/29 [52%] vs 0/14 [0%] in p-PPDS) was pain free at all visits (P = .001). Anterior chamber cell scores were better in the N-PPDS group (patients with no anterior chamber cells: 18/36 [50%] vs 3/16 [19%] in p-PPDS; P = .034) at 7 days. The plug retention rate was 98% (55/56) at 14 days. Adverse events having a suspected relationship with the punctal plug treatment occurred in 1 case of the N-PPDS group having to do with placement and zero in the p-PPDS group. CONCLUSIONS: The N-PPDS was safe and effective for the management of ocular pain and inflammation after cataract surgery.

Assessment of Factors Associated With Postoperative Pain After Photorefractive Keratectomy.

PURPOSE: To define the factors that affect patient's self-assessed postoperative pain after photorefractive keratectomy (PRK). METHODS: Patients who underwent PRK in 2016 were evaluated. Anonymized data collected included patient gender, age, and season at the time of surgery, ablation depth, surgeon status (attending vs. resident), topical tetracaine use, and subjective pain scores at postoperative days (PODs) 1 and 7. Average pain scores and amount of pain medication taken were analyzed for each of the previously mentioned variables. RESULTS: Overall, 231 patients who underwent PRK were analyzed. The mean pain score and SD were 0.78 ± 1.87 on POD 1 and 0.03 ± 0.37 by POD 7. Patients who used topical tetracaine reported significantly higher pain on POD 1 and 7 compared with patients who did not use tetracaine (P < 0.001 and P = 0.038, respectively). No significant differences in pain scores were seen based on surgeon status, ablation depth, gender, and season. Patients who used topical tetracaine took a higher amount of oral pain medication (9.44 ± 6.01) compared with those who did not (7.02 ± 4.71) (P = 0.022). CONCLUSIONS: Postoperative pain was significantly elevated in patients who used tetracaine on POD 1 and POD 7. These patients were also more likely to take oral pain medication than those who did not use topical tetracaine. Surgeon status, season, gender, and ablation depth showed no significant differences in subjective pain scores. Oral pain medication should be evaluated to assess efficacy and safety in inhibiting ocular pain after PRK.

Bandage contact lens use after photorefractive keratectomy.

The use of a bandage contact lens (BCL) immediately after photorefractive keratectomy (PRK) results in less pain. This review analyzed which BCL is most effective in decreasing pain immediately after PRK and evaluated the reepithelialization process in the treated zone. Two databases, PubMed and Medline, were checked for articles published from January 2005 to May 2018. The keywords were photorefractive keratectomy, PRK, contact lens, and bandage contact lens. The review comprised 13 studies; these studies enrolled 842 patients who had PRK. All studies compared the early postoperative results for two types of BCL material (senofilcon A and lotrafilcon A). Of the materials, the pain scores were lowest with a senofilcon A. The size of the defect in the epithelialized area 1 day after surgery decreased fastest with lotrafilcon A.

Deep topical anesthesia with ropivacaine-soaked sponge for phacoemulsification.

PURPOSE: To assess safety and efficacy of deep topical anesthesia with ropivacaine-soaked sponge compared with topical anesthesia with oxybuprocaine in patients undergoing phacoemulsification. METHODS: This was a retrospective study where records of patients operated for cataract were evaluated. Patients using a visual analogue scale scored pain during surgery, and the surgeon on a questionnaire recorded ease of operation. Medical records were evaluated for patients who received topical anesthesia with multiple administrations of oxybuprocaine 0.4% or those who received deep topical anesthesia with a polyvinyl acetal sponge impregnated with ropivacaine 0.75% and positioned under the eyelid 30 min before surgery. RESULTS: A total of one hundred patient records, equally divided in patients receiving deep topical anesthesia or topical anesthesia, were included. The visual analogue scale scores among the groups were statistically significant for a lower pain score in patients who received deep topical anesthesia with ropivacaine-soaked sponges (p = 0.0069). The average surgeon score was significantly higher for the deep topical anesthesia group indicating favorable ease of surgery (p = 0.0341). Six patients had major complications during surgery. No additional anesthesia was necessary to manage the complications in four patients in the deep anesthesia group, whereas propofol was used for the induction and maintenance of anesthesia in two patients in the topical anesthesia group. CONCLUSIONS: Deep topical anesthesia with ropivacaine-soaked sponges performed as well as topical oxybuprocaine regarding safety and efficacy. It provided a lower patient pain score, favorable surgeon satisfaction, and long-lasting anesthesia.

Progesterone Application to the Rat Forehead Produces Corneal Antinociception.

Purpose: Ocular pain and discomfort are the most defining symptoms of dry eye disease. We determined the ability of topical progesterone to affect corneal sensitivity and brainstem processing of nociceptive inputs. Methods: Progesterone or vehicle gel was applied to the shaved forehead in male Sprague Dawley rats. As a site control, gel also was applied to the cheek on the side contralateral to corneal stimulation. Corneal mechanical thresholds were determined using the Cochet-Bonnet esthesiometer in intact and lacrimal gland excision-induced dry eye animals. Eye wipe behaviors in response to hypertonic saline and capsaicin were examined, and corneal mustard oil-induced c-Fos immunohistochemistry was quantified in the brainstem spinal trigeminal nucleus. Results: Progesterone gel application to the forehead, but not the contralateral cheek, increased corneal mechanical thresholds in intact and lacrimal gland excision animals beginning <30 minutes after treatment. Subcutaneous injection of the local anesthetic bupivacaine into the forehead region before application of progesterone prevented the increase in corneal mechanical thresholds. Furthermore, progesterone decreased capsaicin-evoked eye wipe behavior in intact animals and hypertonic saline evoked eye wipe behavior in dry eye animals. The number of Fos-positive neurons located in the caudal region of the spinal trigeminal nucleus after corneal mustard oil application was reduced in progesterone-treated animals. Conclusions: Results from this study indicate that progesterone, when applied to the forehead, produces analgesia as indicated by increased corneal mechanical thresholds and decreased nociceptive responses to hypertonic saline and capsaicin.

Patient Satisfaction with Oral versus Intravenous Sedation for Cataract Surgery: A Randomized Clinical Trial.

PURPOSE: To determine whether patient satisfaction with oral sedation is noninferior to intravenous sedation for cataract surgery. DESIGN: Prospective, randomized, double-masked clinical trial. PARTICIPANTS: A volunteer sample of patients 18 years or older from diverse backgrounds scheduled for cataract surgery. Patients who were allergic to benzodiazepines, older than 70 years with a failed delirium screening questionnaire, pregnant or nursing, using a medication inhibiting cytochrome 450 3A, or intoxicated on the day of surgery were excluded. METHODS: Patients were randomized to receive either oral triazolam with intravenous placebo or intravenous midazolam with oral placebo before surgery. MAIN OUTCOMES MEASURES: The primary outcome was patient satisfaction, measured by a survey administered on postoperative day 1. Secondary outcomes included surgeon and anesthesia provider satisfaction, need for supplemental anesthesia, and surgical complications. RESULTS: Among the 85 patients (42 men [49.4%]; mean age, 65.8 years; standard deviation, 9.5 years) completing the study, the mean satisfaction score was 5.34±0.63 (range, 3.75-6) in the oral sedation group and 5.40±0.52 (range, 4-6) in the intravenous group. With an a priori noninferiority margin of 0.5 and a difference in mean scores between the 2 groups of 0.06 (1-tailed 95% confidence interval [CI], -infinity to 0.27), our results demonstrate noninferiority of oral sedation with a P value of 0.0004. Surgeon and anesthesia provider satisfaction was similar between the 2 groups. Intraoperative complications occurred in 16.7% in the oral group and 9.3% in the intravenous group (difference, 7.4%; 95% CI, -6.9% to 21.6%; P = 0.31). The only major intraoperative complication-a posterior capsular tear-occurred in the intravenous group. Eight patients in the oral group (19.0%) and 3 in the intravenous group (7.0%) received supplemental intravenous sedation (difference, 12.1%; 95% CI, -2.0% to 26.2%; P = 0.097). CONCLUSIONS: The use of oral sedation in cataract surgery has been suggested as a cost- and space-saving measure, potentially allowing the transition of some patients from an operating to procedure room or office-based setting. We report the noninferiority of oral compared with intravenous sedation for cataract surgery in a diverse patient population in terms of patient satisfaction.

Comparison of pain after subepithelial versus conventional accelerated corneal collagen cross-linking for keratoconus.

PURPOSE: To compare the postoperative pain and epithelial healing time in conventional and subepithelial accelerated corneal collagen cross-linking (CXL) for progressive keratoconus. METHODS: The medical records of 27 consecutive patients who underwent accelerated CXL for progressive keratoconus were retrospectively reviewed. Patients were divided into two groups: the conventional (n = 16) and the subepithelial accelerated CXL group (n = 11). Corneal epithelial layers with a diameter of 8.5 mm in central corneas were removed in the conventional group, while epithelial flaps with the same diameter were prepared in the subepithelial group before accelerated CXL procedures. Postoperative pain and epithelial healing time were evaluated within 1 week. RESULTS: No complications developed in the subepithelial group, whereas peripheral corneal sterile infiltrate was observed in three eyes in the conventional group, which disappeared after treated with steroids for a week. The pain of patients in subepithelial group was significantly slighter than those in conventional group, with a significant difference in pain scoring 0, 1, 2 and 3 days postoperatively (P = 0.002, P = 0.001, P = 0.001, P = 0.001, respectively). Different from the fact that patients in subepithelial group had epithelium after operation, the healing time for epithelium in conventional group was 3-6 days, with an average of 4.64 ± 0.59 days. CONCLUSIONS: Subepithelial accelerated CXL significantly improved postoperative pain as well as reduced the epithelial healing time for the treatment of keratoconus.

A randomized controlled trial comparing the efficacy of topical antibiotic steroid combination versus no treatment after fornix-incision strabismus surgery.

PURPOSE: To compare comfort and inflammation in patients treated with postoperative topical antibiotic steroids in one eye versus no treatment in the other eye. METHODS: This prospective, randomized single-masked study included all patients with planned symmetrical strabismus surgery via fornix incision. One eye was randomly assigned to topical postoperative tobramycin-dexamethasone and the other eye was not treated. Patient and parent questionnaires were administered, and two masked observers assessed conjunctival injection over the muscle and wound site. RESULTS: A total of 70 patients completed at least 1 postoperative visit and were included. There was no statistically significant difference between the treatment eye and the no treatment eye in any of the studied parameters. CONCLUSIONS: Postoperative topical antibiotic steroid did not prove to be superior to no treatment in uncomplicated fornix surgery with regard to patient comfort and inflammation. In those cases, consideration may be given to sparing the patient the inconvenience, cost, and potential complications of the topical medication.

Peribulbar anesthesia in sclero-retinal surgery: two quadrants vs single injection.

PURPOSE: To evaluate the advantage of peribulbar anesthesia in two quadrants (infero-temporal and upper nasal) vs single injection technique (infero-temporal) for scleral rhegmatogenous retinal detachment surgery (RRD). PATIENTS AND METHODS: 57 patients, aged between 33 and 75 years (57.01 ± 8.68), waiting for retinal detachment surgery, were randomized in two groups: a group S (29 patients), with single quadrant injection technique and a group C (28 patients) with two quadrants injection. Patients in Group S were injected in two quadrants with a 10 ml mixture containing Mepivacaine 2% 5 ml and Ropivacaine 0.75% 5 ml, with hyaluronidase 10 IU/ ml. Patients in group C were injected with the same anesthetic mixture in one quadrant. Number of additional injection, during surgery, in two groups, were reported. Pain was tested with VAS (Verbal Analogue Scale 0-10) after regional block, when muscles were insulated, during scleral buckling positioning, when conjunctive was closed and 6, 12, 24 hours after surgery. RESULTS: The need for a second peribulbar injection of anesthetic occurred in 9 patients of group C (32.14%); further injection was necessary in 1 patient (3.57%) of group S during scleral buckling (VAS = 7), statistically significant (p <0.05). Postoperative VAS 6 - 12 - 24 hours after surgery was not significant. CONCLUSIONS: The peribulbar anesthesia may be proposed in scleral surgery of retinal detachment; the injection in two quadrants secured solid and satisfactory anesthesia, increasing the outcome of retinal surgery in loco-regional anesthesia.

Contact Lens Solutions and Contact Lens Discomfort: Examining the Correlations Between Solution Components, Keratitis, and Contact Lens Discomfort.

OBJECTIVES: This article will examine the current literature, as it relates to contact lens discomfort (CLD) secondary to contact lens solutions. The reader will better understand the characteristics of contact lenses, as they uniquely interact with each type of contact lens solution and also gain a better comprehension of the components of contact lens solution such as preservatives, surfactants, and chelating agents, which may contribute to discomfort. By investigating corneal staining theory and the mechanisms that contribute to its presence, the reader will gain insight into this clinical finding, which relates to selection of contact lens solutions. The FDA standards for testing solutions and how this relates to contact lens keratitis will also be appraised in regards to current ISO recommendations. Finally, better selection of multipurpose contact lens solution (MPS) and hydrogen peroxide-based solutions for patients should be accessible to the clinician based on this review and preexisting clinical findings or diagnoses. METHODS: A review of current published literature from peer reviewed journals and online journals was conducted to gain an understanding of contact lens solution's impact on contact lens discomfort. CONCLUSIONS: Many studies have been conducted comparing comfort between various types of contact lens solutions. It is challenging to decipher this information and apply it clinically when selecting solutions for patients. By comparing solution components, how contact lens solutions interact with different types of lenses, keratitis related to contact lenses, and preexisting ocular conditions, this review will improve a clinician's ability to eliminate CLD.

Reducing Periorbital Edema and Ecchymosis after Rhinoplasty: Literature Review and Personal Approach.

Postoperative periorbital edema and ecchymosis are most bothersome to rhinoplasty patients. The degree of swelling and bruising is influenced by several factors, and numerous prophylactic and therapeutic measures have been described in the literature. This article reviews the current literature and concludes with the author's suggestions on how to best minimize postoperative periorbital edema and ecchymosis.

Tripolymeric Corneal Coating Gel Versus Balanced Salt Solution Irrigation During Cataract Surgery: A Retrospective Analysis.

PURPOSE: To compare the protective properties and ease of manipulation during cataract surgery of corneal coating with a gel (eyeDRO; AL.CHI.MI.A. S.R.L, Italy) and corneal irrigation with balanced salt solution (BSS). METHODS: We analyzed the data of 51 patients receiving either eyeDRO or BSS during routine cataract surgery performed within a 20-day period in 2016. The selected parameters were intraoperative clarity and ease of manipulation; postoperative epithelial integrity; and patient discomfort. RESULTS: Compared with BSS irrigation, eyeDRO coating significantly increased intraoperative clarity and ease of manipulation (P < 0.01). Single application was required in eyeDRO-treated eyes, whereas BSS was applied 5.3 ± 0.4 times on average (P < 0.01). Two hours postoperatively, a normal epithelium was observed in 90.0% and 60.0% of eyeDRO-coated and BSS-irrigated eyes, respectively; punctate epithelial damage was observed in 9.7% and 40.0% (P < 0.05) of eyeDRO-coated and BSS-irrigated eyes, respectively; eye irritation and foreign body sensation were experienced by 13.0% and 37.0% of eyeDRO-treated patients and by 65.0% and 100% of BSS-treated patients, respectively (P < 0.01). Twenty-four hours postoperatively, 80.0% of BSS-treated patients versus 19.0% of eyeDRO-treated patients still experienced foreign body sensation (P < 0.01). CONCLUSIONS: EyeDRO coating was shown to be a safer and more effective option than BSS irrigation in cataract surgery because single application provided optimal hydration and intraoperative clarity during the entire surgery, better preserved the corneal epithelium, and offered postoperative comfort to the patient.

Evaluation of the Effect of Moist Chamber Spectacles in Patients With Dry Eye Exposed to Adverse Environment Conditions.

PURPOSE: To evaluate the effect of moist chamber spectacle wear on the ocular surface and tear functions in a controlled wind exposure environment. METHODS: Twenty-eight eyes of 14 probable dry eye subjects (4 men, 10 women; mean age: 34.5 years) underwent constant wind exposure for 10 min without spectacle, with conventional spectacle wear, and with moist chamber spectacle wear. Dryness Visual Analog Scale (VAS) scores, tear evaporation, blink rate, tear film breakup testing, and fluorescein staining were performed before and after wind exposure. RESULTS: The mean dryness VAS score after wind exposure was significantly higher when no spectacles were worn or when conventional spectacles with no moist chambers were worn compared with after exposure scores when moist chamber spectacles were worn (P=0.02). The mean of tear evaporation rate from the ocular surface and blink rate increased significantly with wind exposure when no spectacles were worn or when conventional spectacles with no moist chambers were worn (P=0.04). There were no significant changes before and after wind exposure when the moist chamber spectacles were worn (P=0.1). CONCLUSION: Moist chamber spectacles appear to have favorable effects on dry eye symptomatology, tear stability, and blink rates in adverse environment conditions such as wind exposure.

Intraoperative and postoperative pain in cataract surgery.

Technologic improvements in cataract surgery have not only improved visual outcomes, but also have minimized intraoperative and postoperative pain. We review the mechanisms, risk factors, and management of intraoperative and postoperative pain. Summaries of less common sources of physiologic pain have been included to reinforce recognition of when pain represents an expected physiologic reaction to surgery as opposed to signaling a more serious complication. We also discuss various current and emerging anesthetic and analgesic modalities.