Classification of Presbyopia by Severity.

There are close to two billion individuals globally living with presbyopia. In spite of its ubiquitous and progressive nature, there is no widely accepted, formal guideline or consensus statement on the classification of presbyopia by degree of severity. A panel of leading eye care professionals representing both optometrists and ophthalmologists convened virtually to discuss and document their combined assessments from the body of literature and clinical practice expertise in this commentary. In light of emerging therapies, classifying presbyopia by mild, moderate, or advanced severity may help provide consistency of diagnosis among eye care providers and may aid in managing patient expectations with different treatment options.

Advances in Corneal Surgical and Pharmacological Approaches to the Treatment of Presbyopia.

The purpose of this article is to review the current status of presbyopia amelioration with surgical and pharmacologic procedures that partially compensate for loss of accommodation in advance of cataract surgery and lens replacement. Over the last few years, several corneal surgical and topical pharmacological approaches for the treatment of presbyopia have been introduced to the marketplace or are in the developmental pipeline. The approaches vary in invasiveness, duration of effect, reversibility, risk/benefit ratio, and clinical results. The advantages and disadvantages for each are discussed. Corneal surgical interventions aim to provide improved near and intermediate vision in patients with presbyopia through refractive means that extend ocular depth of focus through shape modification. The use of miotic drops or corneal lamellar implants extend depth of focus with the "pinhole" aperture size reduction effect. Unlike in adults younger than 40 years, the refractive status of the patient with presbyopia is not stable. Hence, procedures that provide a permanent refractive change may not provide long-term full correction; eye drops or other treatments that are self-reversing in time or are easily reversible may be used as needed. On the horizon, procedures are being explored that may add years of functional lens accommodation by preserving the deformable gel properties of the lens. [J Refract Surg. 2021;37(6 Suppl):S20-S27.].

Phentolamine Eye Drops Reverse Pharmacologically Induced Mydriasis in a Randomized Phase 2b Trial.

SIGNIFICANCE: After a dilated eye examination, many patients experience symptoms of prolonged light sensitivity, blurred vision, and cycloplegia associated with pharmacological mydriasis. Phentolamine mesylate ophthalmic solution (PMOS) may expedite the reversal of mydriasis in patients, potentially facilitating return to functional vision and reducing barriers to obtaining dilated eye examinations. PURPOSE: The protracted reversal time after pharmacologically induced pupil dilation impairs vision. We tested the hypothesis that PMOS rapidly reduces pupil diameter in this acute indication. METHODS: In this double-masked placebo-controlled, randomized, two-arm crossover phase 2b trial, we evaluated the effects of one drop of 1% PMOS applied bilaterally in subjects who had their pupils dilated by one of two common mydriatic agents: 2.5% phenylephrine or 1% tropicamide. End points included change in pupil diameter, percent of subjects returning to baseline pupil diameter, and accommodative function at multiple time points. RESULTS: Thirty-one subjects completed the study (15 dilated with phenylephrine and 16 with tropicamide). Change in pupil diameter from baseline at 2 hours after maximal dilation with 1% PMOS was -1.69 mm and was significantly greater in magnitude compared with placebo for every time point beyond 30 minutes (P < .05). At 2 hours, a greater percentage of study eyes given 1% PMOS returned to baseline pupil diameter compared with placebo (29 vs. 13%, P = .03), which was this also seen at 4 hours (P < .001). More subjects treated with PMOS in the tropicamide subgroup had at least one eye returning to baseline accommodative amplitude at 2 hours (63 vs. 38%, P = .01). There were no severe adverse events, with only mild to moderate conjunctival hyperemia that resolved in most patients by 6 hours. CONCLUSIONS: Phentolamine mesylate ophthalmic solution at 1% reversed medically induced pupil dilation more rapidly than placebo treatment regardless of which mydriatic was used (adrenergic agonists and cholinergic blockers) with a tolerable safety profile.

Phentolamine Mesylate Ophthalmic Solution Provides Lasting Pupil Modulation and Improves Near Visual Acuity in Presbyopic Glaucoma Patients in a Randomized Phase 2b Clinical Trial.

PURPOSE: Phentolamine mesylate ophthalmic solution (PMOS), applied to the eye topically, was shown previously to have beneficial effects in patients with dim light vision disturbances (DLD), including decreased pupil diameter (PD), improved best-corrected distance visual acuity (BCDVA), as well as lower intraocular pressure (IOP). The ORION-1 trial evaluated the long-term safety and efficacy of PMOS in a glaucomatous, presbyopic population. PATIENTS AND METHODS: In this randomized, double-masked, multi-center, placebo-controlled, multiple-dose Phase 2b trial, 39 patients with elevated IOP were randomized to receive one evening dose of study medication or placebo for 14 days. The primary outcome measure was mean change in diurnal IOP, and the key secondary outcome measures included changes in PD, distance-corrected near visual acuity (DCNVA), and conjunctival hyperemia. RESULTS: Use of 1% PMOS did not lead to a statistically significant decrease in diurnal IOP compared to placebo (P = 0.89) but trended toward a greater decrease in patients with lower IOP baselines. PMOS produced a statistically significant mean 20% PD reduction under both photopic and mesopic conditions that was sustained for 36 hours post-dosing. A statistically significant number of patients with PMOS compared to placebo demonstrated ≥1 line of improvement in photopic DCNVA at day 8 (P = 0.0018), day 15 (P = 0.0072), and day 16 (P = 0.0163), with a trend for 2- and 3-line improvements at all time points. There was no statistical difference in conjunctival hyperemia compared to placebo. CONCLUSION: Although mean IOP was not lowered significantly, daily evening dosing of 1% PMOS was found to be well tolerated with no daytime conjunctival redness and demonstrated improvement in DCNVA with sustained PD reduction in a glaucomatous and presbyopic population. Smaller pupil size can have beneficial effects in improving symptoms of presbyopia and DLD, which will be the focus of further studies.

Treatment outcomes in the DRy Eye Amniotic Membrane (DREAM) study.

PURPOSE: To evaluate the efficacy of cryopreserved amniotic membrane (CAM) in reducing signs and symptoms of dry eye disease (DED) in a large patient population. METHODS: A retrospective chart review at 10 clinical sites was done of patients with refractory DED who received CAM and completed at least 3 months of follow-up. Data collected were demographics; medical history including previous and current ocular treatment, diagnosis, clinical presentations, comorbidity, duration and frequency of treatment with CAM; and concomitant medications. The primary outcome was the change in dry eye workshop (DEWS) score after treatment. RESULTS: A total of 97 eyes of 84 patients exhibited severe dry eye despite maximal medical treatments including topical artificial tears, cyclosporine-A, serum, antibiotics, and steroids. Patients manifested with superficial punctate keratitis (86%), filamentary keratitis (13%), exposure keratitis (19%), neurotrophic keratitis (2%), and corneal epithelial defect (7%). After CAM treatment for 5.4±2.8 days, 74 (88%) patients demonstrated an improved ocular surface along with a notable reduction of the severity as the overall DEWS score was significantly reduced from 3.25±0.5 at baseline to 1.44±0.6 at 1 week, 1.45±0.6 at 1 month, and 1.47±0.6 at 3 months (p<0.001). Ten eyes (10%) required repeated treatment to complete healing. Apart from discomfort during CAM placement, there were no adverse events. CONCLUSION: Placement of CAM is promising to enhance the recovery of ocular surface health and reduce signs and symptoms in patients with moderate-to-severe DED.

The Prospective Health Assessment of Cataract Patients' Ocular Surface (PHACO) study: the effect of dry eye.

PURPOSE: To determine the incidence and severity of dry eye as determined by the International Task Force (ITF) scale in patients being screened for cataract surgery. PATIENTS AND METHODS: This was a prospective, multi-center, observational study of 136 patients, at least 55 years of age, who were scheduled to undergo cataract surgery. The primary outcome measure was the incidence of dry eye as evaluated by grade on the ITF scale and secondary outcome measures include tear break-up time (TBUT), ocular surface disease index score, corneal staining with fluorescein, conjunctival staining with lissamine green, and a patient questionnaire to evaluate symptoms of dry eye. RESULTS: Mean patient age was 70.7 years. A total of 73.5% of patients were Caucasian and 50% were female. Almost 60% had never complained of a foreign body sensation; only 13% complained of a foreign body sensation half or most of the time. The majority of patients (62.9%) had a TBUT ≤5 seconds, 77% of eyes had positive corneal staining and 50% of the eyes had positive central corneal staining. Eighteen percent had Schirmer's score with anesthesia ≤5 mm. CONCLUSION: The incidence of dry eye in patients scheduled to undergo cataract surgery in a real-world setting is higher than anticipated.

Dysfunctional tear syndrome: dry eye disease and associated tear film disorders - new strategies for diagnosis and treatment.

Dysfunctional tear syndrome (DTS) is a common and complex condition affecting the ocular surface. The health and normal functioning of the ocular surface is dependent on a stable and sufficient tear film. Clinician awareness of conditions affecting the ocular surface has increased in recent years because of expanded research and the publication of diagnosis and treatment guidelines pertaining to disorders resulting in DTS, including the Delphi panel treatment recommendations for DTS (2006), the International Dry Eye Workshop (DEWS) (2007), the Meibomian Gland Dysfunction (MGD) Workshop (2011), and the updated Preferred Practice Pattern guidelines from the American Academy of Ophthalmology pertaining to dry eye and blepharitis (2013). Since the publication of the existing guidelines, new diagnostic techniques and treatment options that provide an opportunity for better management of patients have become available. Clinicians are now able to access a wealth of information that can help them obtain a differential diagnosis and treatment approach for patients presenting with DTS. This review provides a practical and directed approach to the diagnosis and treatment of patients with DTS, emphasizing treatment that is tailored to the specific disease subtype as well as the severity of the condition.

Screening Patients With Cataract for Premium IOL Candidacy Using Microperimetry.

PURPOSE: To explore the use of microperimetry in the evaluation of macular dysfunction in patients with cataract, to aid in proper intraocular lens selection (multifocal vs monofocal), and to set expectations for postoperative visual function. METHODS: One randomly chosen eye of 10 patients diagnosed as having mild (1+) to moderate (3+) cataract was evaluated before and 1 week after cataract surgery with the MAIA microperimeter (Centervue S.p.A, Padova, Italy). Corrected distance visual acuity, dilated and undilated biomicroscopy and indirect fundus examinations, intraocular pressure measurement, and a MAIA microperimeter test to measure macular sensitivity and fixation pattern were also performed. RESULTS: Two patients showed macular abnormalities before and after surgery that were noted on MAIA testing: one patient showed reduced average threshold sensitivity and abnormal percent reduced threshold, whereas the other patient showed fixation drift demonstrating eccentric fixation. Both eyes had reduced postoperative visual performance after uneventful cataract surgeries. CONCLUSIONS: Because not every macular lesion noted on fundus examination or optical coherence tomography may be clinically significant, microperimetry can be useful to detect clinically significant retinal dysfunction prior to cataract surgery. The outcome may aid in the selection of intraocular lens type and may yield a better documented surgical prognosis. Further studies are necessary to confirm these findings.

Antibiotic resistance in acute postoperative endophthalmitis.

Acute postoperative endophthalmitis (APE) is a serious, although infrequent, complication of eye surgery that can result in significant morbidity and costs. This review addresses APE risk factors, associated bacterial pathogens, antibiotic resistance, and prevention.

Effect of loteprednol etabonate 0.5% on initiation of dry eye treatment with topical cyclosporine 0.05%.

OBJECTIVE: The purpose of this work was to evaluate the effect of loteprednol etabonate (LE) before the initiation of topical cyclosporine A (tCsA) therapy in patients with mild-to-moderate dry eye disease. Prospective, multicenter randomized double-masked parallel group clinical study (NCT00407043). METHODS: Hundred and eighteen patients with dry eye disease were randomized to receive either LE and tCsA (n=61) or artificial tears (AT) and tCsA (n=57). Hundred and twelve patients completed the study (LE: n=57, AT: n=55) and are included in the data analysis. Patients self-administered either LE or AT for 2 weeks 4 times per day, followed by tCsA twice per day accompanied by either LE twice per day or AT twice per day for an additional 6 weeks of treatment. Primary outcome measures included the Ocular Surface Disease Index (OSDI) questionnaire, the Likert scale using standardized facial expressions, lissamine green staining, fluorescein staining, and the Schirmer test. Additional measures included global self-assessment, and safety outcomes included slitlamp examination, intraocular pressure, and assessment of visual acuity. RESULTS: Loteprednol etabonate pretreatment significantly reduced tCsA stinging (P<0.05). Both groups showed significantly improved OSDI scores at the 14-, 30-, and 60-day visits. Loteprednol etabonate showed significantly more OSDI improvement than AT. Both pretreatment strategies improved global self-assessment scores, Schirmer test, fluorescein staining, lissamine staining, and adjunctive AT use. Loteprednol etabonate showed superior improvement in Schirmer test, fluorescein staining, and lissamine staining. Intraocular pressure did not increase in either group. CONCLUSIONS: Loteprednol etabonate induction therapy 2 weeks before the initiation of long-term tCsA treatment for chronic dry eye disease provides more rapid relief of dry eye signs and symptoms with greater efficacy than tCsA and AT alone.

Safety of besifloxacin ophthalmic suspension 0.6% in refractive surgery: a retrospective chart review of post-LASIK patients.

BACKGROUND: To evaluate the safety of besifloxacin ophthalmic suspension 0.6% when used in laser-assisted in situ keratomileusis (LASIK) prophylactic antibiotic regimens. METHODS: Retrospective surveillance of LASIK surgery cases where besifloxacin ophthalmic suspension 0.6% or moxifloxacin ophthalmic solution 0.5% were prescribed as prophylactic medications. Surgeons from nine US surgical centers provided retrospective case information on surgical outcomes from consecutive cases and reported any adverse events related to the antibacterial used. The primary endpoint was the incidence of adverse drug reactions. RESULTS: A total of 801 case reports (801 eyes; 534 besifloxacin, 267 moxifloxacin) were obtained. The mean (standard deviation [SD]) age at time of surgery was 36.1 (10.6) years. The mean (SD) duration of antibiotic treatment was 8.6 (2.2) days in the besifloxacin group and 8.0 (2.3) in the moxifloxacin group; daily dosing frequency was higher in the moxifloxacin group preoperatively, on the day of surgery, and postoperatively. There were no reports of adverse drug reactions for the 801 eyes in this surveillance. There were no differences between the besifloxacin and moxifloxacin treatment groups in rates of unexpected corneal findings (2.1% vs 1.5%, P = 0.949). The distribution of final visual acuity for the besifloxacin and moxifloxacin groups were similar (P = 0.793). Most cases had a final visual acuity of 20/20 or better. CONCLUSION: In this retrospective surveillance study, the prophylactic use of besifloxacin ophthalmic suspension 0.6% and moxifloxacin ophthalmic solution 0.5% in patients undergoing LASIK surgery was not associated with any adverse drug reactions.

Improving awareness, identification, and management of meibomian gland dysfunction.

Ocular surface disorder--and dry eye, in particular--is a leading reason for visits to eye care professionals. It has been generally accepted that meibomian gland dysfunction (MGD) is a leading cause of evaporative dry eye, as well as being associated with aqueous-deficient dry eye. Yet, researchers and clinicians have lacked a global consensus on the definition of MGD, its epidemiology, pathophysiology, and management. Various systemic diseases and medications have been associated with the progression of both dry eye and MGD, as have several ocular disorders beyond those directly affecting the surface. It is in the best interest of patients for clinicians to be able to better identify and diagnose MGD, differentiating it from other ocular surface disorders, and to recognize the effects of MGD on the ocular surface, and thus initiate appropriate therapy. This CME activity provides expert insight into the Tear Film and Ocular Surface Society's International Workshop on MGD consensus report, offering practical application of its findings to better manage MGD patient care, particularly for those patients facing or undergoing ocular surgery.

Cyclosporine 0.05% to improve visual outcomes after multifocal intraocular lens implantation.

PURPOSE: To evaluate the efficacy of cyclosporine 0.05% in alleviating dry-eye signs and improving visual quality after multifocal intraocular lens (IOL) implantation. SETTING: Private practice and university medical center, New York, New York, USA. METHODS: This randomized prospective contralaterally controlled double-masked trial comprised patients scheduled to have bilateral phacoemulsification with implantation of a refractive multifocal IOL (ReZoom). Patients received twice-daily cyclosporine 0.05% in 1 eye and an artificial tear in the other eye from 1 month before to 2 months after second-eye surgery. Outcomes were evaluated at baseline and 2 months after second-eye surgery. RESULTS: The study enrolled 28 eyes of 14 patients. At baseline, there were no statistically significant between-group differences in outcome measures. Two months postoperatively, the cyclosporine group had significantly lower mean uncorrected distance visual acuity than the artificial tear group (0.11 logMAR +/- 0.03 [SD] [20/25 Snellen equivalent] versus 0.19 +/- 0.05 logMAR [20/30]; P = .045) as well as significantly lower mean corrected distance visual acuity (0.0 +/- 0.02 logMAR [20/20] versus 0.1 +/- 0.02 logMAR [20/25]; P = .005) and corneal staining scores (0.210 +/- 0.07 versus 0.645 +/- 0.18; P = .034). Treatment with cyclosporine 0.05% also improved contrast sensitivity, conjunctival staining, and tear breakup time. Significantly more patients preferred the eye treated with cyclosporine 0.05% to the eye treated with artificial tears (57.1% versus 14.3%; P = .007). CONCLUSION: Cyclosporine 0.05% therapy reduced dry-eye signs and improved visual quality after multifocal IOL implantation. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. Additional disclosures are found in the footnotes.

Efficacy and safety of besifloxacin ophthalmic suspension 0.6% compared with moxifloxacin ophthalmic solution 0.5% for treating bacterial conjunctivitis.

OBJECTIVE: To compare the clinical and antimicrobial efficacy of besifloxacin ophthalmic suspension 0.6% with that of moxifloxacin ophthalmic solution 0.5% for the treatment of bacterial conjunctivitis. DESIGN: Multicenter, randomized, double-masked, parallel-group, active-controlled, noninferiority study. PARTICIPANTS: Patients 1 year of age or older with clinical manifestations of bacterial conjunctivitis. METHODS: Eligible patients were randomized to either besifloxacin suspension or moxifloxacin solution, instilled in the infected eye(s) 3 times daily for 5 days, and participated in study visits on days 1, 5 (+/-1 day), and 8 (+1 day). Assessments included clinical evaluation of signs and symptoms, visual acuity, biomicroscopy, and culture of the infected eye(s) at each visit, as well as direct ophthalmoscopy on days 1 and 8. MAIN OUTCOME MEASURES: The primary efficacy end points were clinical resolution and microbial eradication of baseline bacterial infection on day 5 in patients with culture-confirmed bacterial conjunctivitis. Secondary end points included clinical resolution and microbial eradication on day 8, individual clinical outcomes, microbial and clinical outcomes by bacterial species, and safety. RESULTS: A total of 1161 patients (533 with culture-confirmed bacterial conjunctivitis) were randomized. Based on the 95% confidence interval (CI) of the difference, besifloxacin was noninferior to moxifloxacin for clinical resolution on day 5 (58.3% vs. 59.4%, respectively; 95% CI, -9.48 to 7.29) and day 8 (84.5% vs. 84.0%, respectively, 95% CI, -5.6% to 6.75%) and for microbial eradication on day 5 (93.3% vs. 91.1%, respectively, 95% CI, -2.44 to 6.74) and day 8 (87.3% vs. 84.7%; 95% CI, -3.32 to 8.53). There was no statistically significant difference between the 2 treatment groups for either efficacy end points on days 5 or 8 (P>0.05). Besifloxacin and moxifloxacin were well tolerated. The cumulative frequency of ocular adverse events was similar between treatments (12% and 14% with besifloxacin and moxifloxacin, respectively). However, eye irritation occurred more often in moxifloxacin-treated eyes (0.3% for besifloxacin vs. 1.4% for moxifloxacin; P = 0.0201). CONCLUSIONS: Besifloxacin ophthalmic suspension was non inferior to moxifloxacin ophthalmic suspension and provided similar safety and efficacy (clinical and microbiological) outcomes when used for the treatment of bacterial conjunctivitis. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Intracorneal inlay for the surgical correction of presbyopia.

PURPOSE: To evaluate the clinical safety and efficacy of the ACI-7000 intracorneal inlay in increasing the depth of field in emmetropic presbyopic patients. SETTING: Beyoglu Eye Research and Education Hospital, Istanbul, Turkey. METHODS: This prospective unmasked study comprised 39 presbyopic patients; 12 were naturally emmetropic and 27 had emmetropia resulting from previous hyperopic laser in situ keratomileusis. The intracorneal inlay was placed over the pupil in the patient's nondominant eye after flap lift or creation of a conventional flap using a microkeratome. The inlay was centered on the visual axis. Postoperative follow-up was 1 year. RESULTS: Of the 39 inlays implanted, 3 were explanted during the study. At 1 year, the mean uncorrected near visual acuity improved from J6 (preoperatively) to J1+. All eyes with an inlay had an uncorrected near acuity of J3 or better and 85.3%, of J1 or better. Binocularly, the mean uncorrected near acuity remained J1 or better throughout the study. The mean uncorrected distance visual acuity in eyes with an inlay did not change significantly from preoperatively and remained 20/20 throughout the study period. All 3 eyes with inlay explantation returned to within +/-1.00 diopter of the preoperative refractive state for near and distance vision, with no loss of best corrected distance visual acuity. CONCLUSION: The ACI-7000 intracorneal inlay showed the potential to provide safe, effective, and reversible treatment of presbyopia.

Safety and efficacy of cyclosporine 0.05% drops versus unpreserved artificial tears in dry-eye patients having laser in situ keratomileusis.

PURPOSE: To evaluate dry-eye signs, symptoms, and refractive outcomes in patients with dry-eye disease having laser in situ keratomileusis (LASIK). METHODS: In this randomized parallel double-masked prospective clinical trial, 42 eyes of 21 myopic patients (mean spherical equivalent -4.3 diopters [D], range -1.00 to -10.63 D) with dry-eye disease were treated with unpreserved artificial tears or cyclosporine 0.05% ophthalmic emulsion twice a day beginning 1 month before LASIK. Treatment with the study drug was discontinued for 48 hours post surgery and then resumed for 3 additional months. Both groups used additional artificial tears as needed. Study visits occurred pretreatment (baseline), before surgery, and at 1 week and 1, 3, 6, and 12 months after surgery. RESULTS: Statistically significant increases from baseline were found in Schirmer scores for artificial tears at 1 month (P = .036) and for cyclosporine 0.05% before surgery and 1 week, 1 month, and 6 months after surgery (P<.018). There were no significant differences from baseline or between groups in responses to the Ocular Surface Disease Index questionnaire or best corrected visual acuity (BCVA), nor were there significant between-group differences in superficial punctate keratitis or uncorrected visual acuity. Mean refractive spherical equivalent in cyclosporine-treated eyes was significantly closer to the intended target at 3 and 6 months after surgery than in artificial-tears-treated eyes (P = .007). A greater percentage of cyclosporine eyes was within +/-0.5 D of the refractive target 3 months after surgery than artificial tears eyes (P = .015). CONCLUSION: Successful outcomes after LASIK were achieved for dry-eye disease patients. Treatment with cyclosporine 0.05% provided greater refractive predictability 3 and 6 months after surgery than unpreserved artificial tears.

Safety and efficacy of levofloxacin 1.5% eyedrops in nonhuman primates having penetrating keratoplasty: clinical and laboratory findings.

PURPOSE: To determine the safety and efficacy of levofloxacin 1.5% eyedrops. SETTING: Tulane University Delta Research Primate Center, New Orleans, Louisiana, USA. METHODS: Ten monkeys had preoperative slitlamp examinations, photographs, and confocal microscopy. Levofloxacin 1.5% or control eyedrops were given 4 times a day in both eyes for 2 days and every 5 minutes for the hour before surgery and 4 times a day in both eyes for 1 week. Confocal microscopy, slitlamp examination, and slitlamp photography were repeated preoperatively. Intraoperative aqueous humor and corneal biopsies were taken. RESULTS: There were no differences between groups in slitlamp examinations, slitlamp photography, confocal microscopy, or histology; the mean levofloxacin level in the aqueous humor was 4.49 mug/mL +/-1.59 SD and in the corneal biopsies, 103.85 +/- 51.48 mug/g. CONCLUSION: Levofloxacin 1.5% drops given on a typical perioperative schedule to monkeys having penetrating keratoplasty showed no clinical or histological signs of toxicity and reached corneal issue levels well over the minimum inhibitory concentrations for all known ocular pathogens.