Nepafenac 0.3% after Cataract Surgery in Patients with Diabetic Retinopathy: Results of 2 Randomized Phase 3 Studies.

PURPOSE: To demonstrate the efficacy and safety of once-daily nepafenac 0.3% ophthalmic suspension versus vehicle, based on clinical outcomes, after cataract surgery in patients with diabetes. DESIGN: Two prospective, randomized, multicenter, double-masked, vehicle-controlled phase 3 studies. PARTICIPANTS: Total, 615 patients in study 1 and 605 patients in study 2. METHODS: Patients were randomized (1:1) to topical nepafenac 0.3% or vehicle once-daily starting the day before surgery and continuing for 90 days thereafter. MAIN OUTCOME MEASURES: Key efficacy variables were: patients (%) in whom macular edema (ME) developed (≥30% increase from preoperative baseline central subfield macular thickness) within 90 days after cataract surgery and the patients (%) with a best-corrected visual acuity (BCVA) improvement of ≥15 letters from preoperative baseline through day 14 maintained through day 90. Secondary end points included: patients (%) with a BCVA improvement of ≥15 letters from preoperative baseline through days 90 and 60 and safety over 3 months. RESULTS: A significantly lower percentage of patients demonstrated ME within 90 days after surgery with nepafenac 0.3% versus vehicle (study 1: 2.3% vs. 17.3%; P < 0.001; study 2: 5.9% vs. 14.3%; P = 0.001; pooled: 4.1% vs. 15.9%; P < 0.001). The percentage of patients achieving a ≥15-letter improvement from baseline through day 14 maintained through day 90 with nepafenac 0.3% versus vehicle was 61.7% versus 43.0% (P < 0.001) in study 1, 48.8% versus 50.5% (P = 0.671) in study 2, and 55.4% versus 46.7% (P = 0.003) in the pooled analysis. A greater percentage of patients treated with nepafenac 0.3% versus vehicle in study 1 and similar percentage in study 2 had a BCVA improvement of ≥15 letters from preoperative baseline through day 90 (77.2% vs. 67.7% [P = 0.009] and 65.4% vs. 65.9% [P = 0.888]) and through day 60 (76.2% vs. 64.7% [P = 0.002] and 68.9% vs. 62.1% [P = 0.092]). No unanticipated adverse events were observed. CONCLUSIONS: These studies demonstrated the clinical benefits of nepafenac 0.3% over vehicle in reducing the risk of postoperative ME, with the integrated analysis showing improved BCVA after cataract surgery in patients with diabetic retinopathy, with no unanticipated safety events.

Complete response and long-term survival (>20 years) of a child with tectal glioma: a case report.

Tectal glioma is a midbrain tumor. The patient generally presents with symptoms related to increased intracranial pressure and requires treatment for hydrocephalus. No effective pharmacological treatments have yet been introduced. This report discusses a case of a 13-year-old male diagnosed with tectal glioma who obtained a complete response and long-term survival after the treatment with antineoplastons (ANP) in phase II trial. Prior treatment consisted of placement of a ventriculoperitoneal shunt. After 6 years of stabilization there had been an increase in tumor size with signs of malignant transformation. The patient received treatment with ANP A10 and AS2-1 infusions for 20 months, obtained a complete response, and was switched to maintenance with ANP capsules. All treatments were discontinued in December 2003. Adverse events according to CTCAE v3.0 included: hypernatremia (two events of grade 3, one event of grade 2, four events of grade 1), one case of fatigue (grade 2), and one allergic reaction (grade 1). Currently, over 20 years from his diagnosis and over 13 years from treatment start he is symptom-free and leads a normal life. This report indicates that it is possible to obtain long-term survival of a child with tectal glioma with currently available investigational treatment.

The relationship of glucokinase activator-induced hypoglycemia with arteriopathy, neuronal necrosis, and peripheral neuropathy in nonclinical studies.

Glucokinase activators (GKAs) are being developed for the treatment of type 2 diabetes. The toxicity of 4 GKAs (PF-04279405, PF-04651887, piragliatin, and PF-04937319) was assessed in mice, rats, dogs, and/or monkeys. GKAs were administered for 2 to 8 weeks. Standard endpoints, glucose, and insulin were assessed. All compounds produced varying degrees of hypoglycemia in all species. Brain neuronal necrosis and/or peripheral neuropathy were observed with most compounds. These findings are consistent with literature reports linking hypoglycemia with nervous system effects. Arteriopathy, mainly of cardiac vessels, was observed at a low frequency in monkey and/or dog. Arteriopathy occurred only at doses that produced severe and prolonged periods of repeated hypoglycemia. Since this lesion occurred in multiple studies with structurally distinct GKAs, these results suggested arteriopathy was related to GKA pharmacology. The morphological characteristics of the arteriopathy were consistent with that produced by experimental catecholamine administration. We hypothesize that the prolonged periods of hypoglycemia resulted in increased local and/or systemic concentrations of catecholamines via a counterregulatory and/or stress-related mechanism. Alternatively, prolonged hypoglycemia may have resulted in endothelial dysfunction leading to arteriopathy. This risk can be managed in human patients in clinical studies by careful glucose monitoring and intervention to avoid prolonged episodes of hypoglycemia.

The response and survival of children with recurrent diffuse intrinsic pontine glioma based on phase II study of antineoplastons A10 and AS2-1 in patients with brainstem glioma.

BACKGROUND: Brainstem gliomas (BSG) are relatively rare tumors of which recurrent pediatric diffuse intrinsic pontine gliomas (RPDIPG) comprise a distinct group. Numerous trials have been conducted on RPDIPG, none of which have resulted in identifying any proven pharmacological treatment benefit. This study included 40 patients diagnosed with different types of BSG, but it was decided to describe first the encouraging results in the most challenging group of RPDIPG. MATERIALS AND METHODS: This single-arm phase II study evaluated the efficacy and safety of the combination of antineoplastons A10 and AS2-1 (ANP) in patients with RPDIPG. Seventeen patients (median age 8.8 years) were enrolled, and all were diagnosed with RPDIPG. ANP was administered intravenously daily. Efficacy analyses were conducted in this group of patients. RESULTS: In this group, complete responses were observed in 6 % of patients, partial responses in 23.5 %, and stable disease in 11.8 %. Six-month progression-free survival was 35.3 %. One-year overall survival was 29.4 %, 2 years 11.8 %, and 5, 10, and 15 years 5.9 %. One patient with DIPG is alive over 15 years post-treatment. Grade 3 and higher toxicities including hypokalemia and fatigue occurred in 6 %, hypernatremia in 18 %, fatigue and urinary incontinence in 6 %, and somnolence in 12 %. In a single patient, grade 4 hypernatremia occurred when he was on mechanical ventilation. He was disconnected from the ventilator and died from brain tumor according to the attending physician. Responding patients experienced improved quality of life. CONCLUSION: The results suggest that ANP shows efficacy and acceptable tolerability profile in patients with RPDIPG.

Lipoamide channel-binding sulfonamides selectively inhibit mycobacterial lipoamide dehydrogenase.

Tuberculosis remains a global health emergency that calls for treatment regimens directed at new targets. Here we explored lipoamide dehydrogenase (Lpd), a metabolic and detoxifying enzyme in Mycobacterium tuberculosis (Mtb) whose deletion drastically impairs Mtb's ability to establish infection in the mouse. Upon screening more than 1.6 million compounds, we identified N-methylpyridine 3-sulfonamides as potent and species-selective inhibitors of Mtb Lpd affording >1000-fold selectivity versus the human homologue. The sulfonamides demonstrated low nanomolar affinity and bound at the lipoamide channel in an Lpd-inhibitor cocrystal. Their selectivity could be attributed, at least partially, to hydrogen bonding of the sulfonamide amide oxygen with the species variant Arg93 in the lipoamide channel. Although potent and selective, the sulfonamides did not enter mycobacteria, as determined by their inability to accumulate in Mtb to effective levels or to produce changes in intracellular metabolites. This work demonstrates that high potency and selectivity can be achieved at the lipoamide-binding site of Mtb Lpd, a site different from the NAD⁺/NADH pocket targeted by previously reported species-selective triazaspirodimethoxybenzoyl inhibitors.

Alkali-treated penicillin G solution is a better option than penicillin G as an alternative source of minor determinants for penicillin skin test.

Both benzylpenicilloyl-polylysine (PPL) and minor determinant mixture (MDM) are the recommended standard reagents for penicillin skin testing. However, penicillin G is commonly suggested as an alternative source of minor determinants. This study evaluated the accuracy of penicillin G and alkali-treated penicillin G compared with the standardized MDM for skin testing. Sixty-eight patients with histories of allergies to penicillin or semisynthetic penicillins were skin tested with commercial Kit penicillin allergenic determinants (DAP) (PPL and DAP-MDM; Diater Laboratorios, Madrid, Spain). The in-house MDM (IH-MDM), prepared by alkali-treated aged penicillin, and fresh penicillin G sodium (PGs) were tested alongside DAP-MDM. Positive penicillin skin test results were identified in 22 patients (32.4%) using commercial reagents (PPL+ DAP-MDM) and 19 of them reacted to DAP-MDM alone or together with PPL. The accuracy of IH-MDM and PGs compared with DAP-MDM was 89.7 and 76.5%, respectively. Our study shows that alkali-treated penicillin G is a better option than penicillin G as an alternative source of MDM for skin testing in case the commercialized MDM is not available. Minor determinants play a significant role for penicillin allergy in Thailand and should be included in the penicillin skin test panel to verify suspected cases of penicillin allergy. (ClinicalTrials.gov number: NCT00789217).

5-Fluorouracil Enhances the Antitumor Activity of the Glutaminase Inhibitor CB-839 against PIK3CA-Mutant Colorectal Cancers.

PIK3CA encodes the p110α catalytic subunit of PI3K and is frequently mutated in human cancers, including ∼30% of colorectal cancer. Oncogenic mutations in PIK3CA render colorectal cancers more dependent on glutamine. Here we report that the glutaminase inhibitor CB-839 preferentially inhibits xenograft growth of PIK3CA-mutant, but not wild-type (WT), colorectal cancers. Moreover, the combination of CB-839 and 5-fluorouracil (5-FU) induces PIK3CA-mutant tumor regression in xenograft models. CB-839 treatment increased reactive oxygen species and caused nuclear translocation of Nrf2, which in turn upregulated mRNA expression of uridine phosphorylase 1 (UPP1). UPP1 facilitated the conversion of 5-FU to its active compound, thereby enhancing the inhibition of thymidylate synthase. Consistently, knockout of UPP1 abrogated the tumor inhibitory effect of combined CB-839 and 5-FU administration. A phase I clinical trial showed that the combination of CB-839 and capecitabine, a prodrug of 5-FU, was well tolerated at biologically-active doses. Although not designed to test efficacy, an exploratory analysis of the phase I data showed a trend that PIK3CA-mutant patients with colorectal cancer might derive greater benefit from this treatment strategy as compared with PIK3CA WT patients with colorectal cancer. These results effectively demonstrate that targeting glutamine metabolism may be an effective approach for treating patients with PIK3CA-mutant colorectal cancers and warrants further clinical evaluation. SIGNIFICANCE: Preclinical and clinical trial data suggest that the combination of CB-839 with capecitabine could serve as an effective treatment for PIK3CA-mutant colorectal cancers.

Effects of topical nepafenac on corneal epithelial healing time and postoperative pain after PRK: a bilateral, prospective, randomized, masked trial.

PURPOSE: To assess the effects of nepafenac on corneal epithelial healing time and pain control compared to placebo in patients undergoing photorefractive keratectomy (PRK) surgery. METHODS: This randomized, double-masked, placebo-controlled, single-site study included 66 adults (132 eyes) undergoing bilateral PRK surgery. Patients received 1 drop three times daily of nepafenac 0.1% in one eye and balanced salt solution in the contralateral eye until the corneal epithelium healed. Postoperatively, patients were evaluated daily for the progression of epithelial healing until complete closure was observed. Patients also were asked daily to assess the level of pain in each eye using a visual analog scale of 0 to 10. RESULTS: There was no statistical difference between treatments in time to epithelial healing. All patients healed by postoperative day 4. Patients receiving nepafenac reported significantly less pain on postoperative days 1 (0.76 versus 1.68) and 2 (1.26 versus 2.23) compared to placebo (P<.0005). A greater percentage of patients also reported superior pain relief in the nepafenac-treated eye compared to the placebo eye during the first 3 days following surgery. CONCLUSIONS: Treatment with nepafenac 0.1% significantly reduced postoperative pain immediately following surgery and had no significant adverse effect on time to reepithelialization compared to placebo.

Intracameral Use of Nepafenac: Safety and Efficacy Study.

PURPOSE: To test the intracameral safety of nepafenac and its efficacy in inhibiting prostaglandin synthesis during phacoemulsification surgery. METHODS: The safety evaluation was conducted in normal eyes of rabbits, 0.1ml of 0.3% and 1% nepafenac was injected intracamerally. Extensive studies to detect adverse response ranged from a gross examination of eyes under slit lamp biomicroscope, fluorescein dye test, Schirmer tear test, test for corneal sensitivity, intraocular pressure measurement (IOP), specular microscopy, electroretinography(ERG), and histopathological examination of intraocular tissues. Efficacy of nepafenac was studied by intracameral injection of 0.1%, 0.3% nepafenac, nepafenac 0.3%+1% lignocaine, and 1% lignocaine alone, before phacoemulsification surgery and intraoperative mydriasis along with PGE2(ProstaglandinE2) secretion were recorded. RESULTS: Single 0.1ml of 0.3% or 1% nepafenac did not significantly (p > 0.05) alter physiological parameters and histology of cornea, iris, and retina. Nepafenac 0.3% effectively inhibited PGE2 secretion. No significant (p > 0.05) prevention of miosis was recorded with 0.1% or 0.3% nepafenac. However, a combination of 0.3% nepafenac + 1% lignocaine and 1% lignocaine alone significantly (p < 0.05) arrested miosis during the intraoperative period. CONCLUSION: An intracameral concentration of up to 1% nepafenac does not adversely affect the rabbit eye. Nepafenac fails to prevent miosis but inhibits prostaglandin release during phacoemulsification surgery.

Nepafenac-associated corneal melt.

We describe a patient with systemic graft-versus-host disease who developed a nonhealing epithelial defect after cataract surgery that healed on cessation of a topical nonsteroidal antiinflammatory drug (NSAID) (ketorolac). The patient developed a central corneal perforation in the fellow eye while on a new NSAID formulation (nepafenac) after routine cataract surgery. Our case suggests that new topical NSAIDs may be similar to older NSAID formulations in promoting corneal melting in patients predisposed to poor epithelialization and corneal wound healing.

Ketorolac tromethamine LS 0.4% versus nepafenac 0.1% in patients having cataract surgery. Prospective randomized double-masked clinical trial.

PURPOSE: To compare the clinical, subjective, and objective outcomes of the use of 2 topical nonsteroidal antiinflammatory drugs--ketorolac tromethamine LS 0.4% (Acular) and nepafenac 0.1% (Nevanac)--in patients having cataract surgery. SETTING: Single-center private practice, Las Vegas, Nevada, USA. METHODS: One hundred eighty-three patients (193 eyes) with visually significant cataract were recruited for the study. Consenting patients were randomized to a standard regimen of Acular, gatifloxacin 0.3% (Zymar), and prednisolone acetate 1% (Pred Forte) (ketorolac group) or Nevanac, moxifloxacin hydrochloride 0.5% (Vigamox), and prednisolone acetate (Econopred) (nepafenac group). Analysis included subjective complaints (burning, itching, foreign-body sensation, pain level after surgery) and objective findings (visual function, degree of inflammation in the anterior segment, complications). RESULTS: The ketorolac group consisted of 94 patients (100 eyes) and the nepafenac group, 89 patients (93 eyes). The between-group differences in visual outcomes and anterior chamber inflammation were not statistically significant (mean P = .33). There was a higher incidence of posterior capsule opacification in the nepafenac group (P = 0.019). Patient satisfaction, patient compliance, and postoperative pain control were statistically significantly better in the ketorolac group (P = .022, P = .023, and P = .025, respectively). CONCLUSION: Ketorolac tromethamine was statistically significantly better than nepafenac in terms of patient satisfaction, compliance, and postoperative pain control.

Case of corneal melting associated with the use of topical nepafenac.

PURPOSE: To report a case of corneal melting associated with the use of the topical nonsteroidal anti-inflammatory agent Nepafenac. METHODS: Case report and literature review. RESULTS: A 62-year-old woman with a complicated ocular history developed corneal melting associated with the use of Nepafenac. On discontinuation of Nepafenac, the melt rapidly resolved. CONCLUSIONS: Topical nonsteroidal anti-inflammatory agents have been associated with corneal ulceration and stromal melts. This is, to our knowledge, the first reported case involving the new agent, Nepafenac.

Double-masked comparison of ketorolac tromethamine 0.4% versus nepafenac sodium 0.1% for postoperative healing rates and pain control in eyes undergoing surface ablation.

PURPOSE: Determine the degree of postoperative pain and rate of healing in eyes treated with either ketorolac tromethamine 0.4% (Acular LS) or nepafenac sodium 0.1% (Nevanac) after flapless surface ablation [epi-laser in situ keratomileusis (LASIK)]. METHODS: Prospective, randomized, double-masked, paired-eye comparison. Patients undergoing flapless surface ablation were randomized to receive ketorolac in 1 eye and nepafenac in the other. Drops were instilled immediately after the surgical procedure, and patients continued to instill the masked drops 3 times daily for 5 days. Study follow-up visits were at days 1 and 5 postoperatively. Patients were queried by phone regarding their level of pain at 5 hours postoperatively and on days 2, 3, and 4. Outcome measures included postoperative pain levels including need for additional rescue medications, rate of healing, and adverse events. RESULTS: Although the original target population was 60 eyes of 30 patients, this study was halted after only 14 eyes of 7 patients because of concern for patient safety, because most patients in 1 arm developed haze. Eyes treated with nepafenac healed at a slower rate than eyes treated with ketorolac in 57% of patients. Mean time to healing was 5.7 +/- 1.1 days with ketorolac and 7.9 +/- 2.1 days with nepafenac (P = 0.066). Moreover, eyes treated with nepafenac exhibited statistically significant greater mean hazing scores at week 2 (P = 0.024) and month 1 (P = 0.039). Throughout the study, a greater percentage of nepafenac-treated eyes exhibited haze than did ketorolac-treated eyes. This difference was statistically significant at week 2 (P = 0.005) and month 1 (P = 0.039). Patients reported significantly more pain in nepafenac-treated eyes at day 3 when pain was at its peak (P = 0.046). CONCLUSIONS: In patients undergoing epi-LASIK, a statistically significant trend postoperative toward increased corneal haze was seen with nepafenac compared with ketorolac. Nepafenac therapy resulted in a non-statistically significant trend toward delayed healing. The study was halted because of safety concerns.

Comparison of the efficacy and patients' tolerability of Nepafenac and Ketorolac in the treatment of ocular inflammation following cataract surgery: A meta-analysis of randomized controlled trials.

As a new ophthalmic non-steroidal anti-inflammatory drug (NSAID) with prodrug structure, Nepafenac was supposed to have a better efficacy than conventional NSAIDs both in patients' tolerability and ocular inflammation associated with cataract surgery. However, many current studies reached contradictory conclusions on the superiority of Nepafenac over Ketorolac. The objective of our study is to evaluate the efficacy and patients' tolerability of Nepafenac and Ketorolac following cataract surgery. To clarify this, we conducted a meta-analysis of randomized controlled trials. Eleven articles were included in this study. The dataset consisted of 1165 patients, including 1175 cataract surgeries. Among them, 574 patients were in the Nepafenac group and 591 in the Ketorolac group. Our analysis indicated that these two drugs were equally effective in controlling post cataract surgery ocular inflammation, reducing macular edema, achieving a better visual ability and maintaining intraoperative mydriasis during cataract surgery. However, Nepafenac was more effective than Ketorolac in reducing the incidence of postoperative conjunctival hyperemia and ocular discomfort. This meta-analysis indicated that topical Nepafenac is superior to Ketorolac in patients' tolerability following cataract surgery. However, these two drugs are equally desirable in the management of anterior chamber inflammation, visual rehabilitation and intraoperative mydriasis. Given the limitations in our study, more researches with larger sample sizes and focused on more specific indicators such as peak aqueous concentrations of drugs or PEG2 levels are required to reach a firmer conclusion.

Targeted therapy with antineoplastons A10 and AS2-1 of high-grade, recurrent, and progressive brainstem glioma.

BACKGROUND: Brainstem glioma carries the worst prognosis of all malignancies of the brain. Most patients with brainstem glioma fail standard radiation therapy and chemotherapy and do not survive longer than 2 years. Treatment is even more challenging when an inoperable tumor is of high-grade pathology (HBSG). The objective of this report is to summarize the outcome of patients with HBSG treated with antineoplastons in 4 phase 2 trials. PATIENTS: The following group of 18 patients was evaluable: 4 patients with glioblastomas and 14 patients with anaplastic HBSG. Fourteen patients had diffuse intrinsic tumors. Twelve patients suffered from recurrence, and 6 patients did not have radiation therapy or chemotherapy. METHODS: Antineoplastons, which consist of antineoplaston A10 (A10I) and AS2-1 injections, were given in escalating doses by intravenous injections. The median duration of antineoplaston administration was 5 months, and the average dosage of A10I was 9.22 g/kg/d and of AS2-1 was 0.31 g/kg/d. Responses were assessed by gadolinium-enhanced magnetic resonance imaging and positron emission tomography. RESULTS: The overall survival at 2 and 5 years was 39% and 22%, respectively, and maximum survival was more than 17 years for a patient with anaplastic astrocytoma and more than 5 years for a patient with glioblastoma. Progression-free survival at 6 months was 39%. Complete response was achieved in 11%, partial response in 11%, stable disease in 39%, and progressive disease in 39% of patients. Antineoplastons were tolerated very well with 1 case of grade 4 toxicity (reversible anemia). CONCLUSION: Antineoplastons contributed to more than a 5-year survival in recurrent diffuse intrinsic glioblastomas and anaplastic astrocytomas of the brainstem in a small group of patients.

Effects of piragliatin, a glucokinase activator, on fasting and postprandial plasma glucose in patients with type 2 diabetes mellitus.

To assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of piragliatin, a double-blind, randomized, placebo-controlled, multiple-ascending-doses study was conducted in patients with type 2 diabetes mellitus (T2D). Fifty-nine T2D patients were given piragliatin or placebo in a dose-escalation design as a single dose on day 1 followed by multiple doses on days 3 through 8 at doses of 10, 25, 50, 100, and 200 mg twice a day (BID) as well as 200 mg every day (QD). Blood and urine samples were collected for PK analysis. PD assessments included plasma glucose, insulin, C-peptide, glucagon, and GLP-1. Piragliatin exposure was dose proportional without appreciable accumulation or food effect. Piragliatin treatment at steady state yielded dose-dependent reductions up to 32.5% and 35.5% for the highest dose in fasting and postprandial plasma glucose. Piragliatin was well tolerated. Mild or moderate hypoglycemia with rapid recovery after sugar-containing drinks or scheduled meals was the only dose-limiting adverse event. It is concluded that multiple doses of piragliatin consistently showed rapid, dose-dependent glucose reduction of fasting and postprandial plasma glucose in T2D patients.

Pharmacokinetic and Pharmacodynamic Drug Interaction Study of Piragliatin, a Glucokinase Activator, and Glyburide, a Sulfonylurea, in Type 2 Diabetic Patients.

A glucokinase activator and a sulfonylurea might be coprescribed to synergize treatment success for type 2 diabetes (T2D). This clinical pharmacology study was designed to investigate the potential glucose-lowering effect or pharmacodynamic (PD), pharmacokinetic (PK), and safety/tolerability interactions between piragliatin and glyburide in T2D patients already taking glyburide but not adequately controlled. This was an open-label, multiple-dose, 3-period, single-sequence crossover design: on days -1, 6, and 12, PD and PK samples were drawn with glyburide alone (period 0), piragliatin + glyburide (period 1), and piragliatin alone (period 2) treatments. The glucose-lowering effect, including fasting plasma glucose (FPG), of piragliatin was more pronounced when it was administered concomitantly with glyburide as compared to piragliatin or glyburide administered alone. However, this enhancement cannot be explained by a potential PK interaction between piragliatin and glyburide. Other than hypoglycemia, there were no clinically relevant safety findings. Thus, the enhanced PD effect warrants further investigation to define the optimal dose combination between glucokinase activators and sulfonylureas with regard to efficacy, safety, and tolerability.

Comparison of the Tolerability of Diclofenac and Nepafenac.

PURPOSE: Topical nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for the prevention and treatment of inflammation and pain following cataract surgery. Preservative-free diclofenac and nepafenac drops are commonly used ophthalmic NSAIDs. The purpose of this study was to compare the tolerability of diclofenac to that of nepafenac. METHODS: In this prospective patient-blinded study, consecutive patients undergoing cataract surgery were included. One drop of nepafenac 0.1% and diclofenac sodium 0.1% were instilled in the right and left eyes, respectively, one immediately after the other, 1 day before surgery. Visual analog scale (scale 0-10) was used to measure patient discomfort, itching, burning, and pain at 1 second (s), 15 s, 1 minute (min), and 5 min postadministration. RESULTS: Overall, 44 eyes of 22 patients were included in this study. Diclofenac and nepafenac had high and similar tolerability at all time points with no significant difference regarding all aspects of tolerability. A vast majority of patients (72%) did not prefer 1 drop over the other in terms of overall comfort. CONCLUSIONS: Both diclofenac and nepafenac seem to have similar high tolerability. Diclofenac may be an affordable alternative to nepafenac and therefore should be considered by prescribing physicians, specifically in preoperative cataract patients.