<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02973880</url>
  </required_header>
  <id_info>
    <org_study_id>044-SI</org_study_id>
    <secondary_id>2016-002138-63</secondary_id>
    <nct_id>NCT02973880</nct_id>
  </id_info>
  <brief_title>Clinical Study to Evaluate the Efficacy and Tolerability of an Anti-inflammatory/Antibiotic Treatment Following Ocular Cataract Extraction</brief_title>
  <official_title>A Prospective, Multi-center, Controlled, Double-blind Study to Evaluate the Efficacy and Tolerability of a Steroid/Antibiotic Associated Treatment Following Cataract Extraction by Means of Phaco-emulsification</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>SIFI SpA</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sintesi Research Srl</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>SIFI SpA</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cataract is an ophthalmic disease that usually affects the elderly population. Cataract&#xD;
      surgery with phaco-emulsification is now the most frequently performed intraocular surgical&#xD;
      procedure in the developed world. However, differences in surgical technique impact the&#xD;
      severity of surgical trauma and post-operative recovery. The amount of post-operative ocular&#xD;
      pain and inflammation plays a significant role in the Patient's perception of the surgical&#xD;
      success.&#xD;
&#xD;
      Several ophthalmic products have been studied in the management of post-surgery ocular&#xD;
      inflammation and pain following cataract surgery. Corticosteroids are considered the gold&#xD;
      standard for the treatment of ocular inflammation, and their most commonly used route of&#xD;
      administration is the topical instillation as eye drops formulation.&#xD;
&#xD;
      After topical administration of Dexamethasone, the concentration in the anterior chamber&#xD;
      increases and declines within hours, necessitating frequent daily instillations of eye drops&#xD;
      for several weeks. This might be associated with compliance issues, particularly in elderly&#xD;
      Patients or in individuals with disabilities. A pharmaceutical formulation allowing for a&#xD;
      less frequent administration could therefore be an attractive alternative.&#xD;
&#xD;
      NETILDEX™ eye drops solution, containing Netilmicin Sulfate 4.55 mg (3mg/ml) and&#xD;
      Dexamethasone Disodium Phosphate 1.32 mg (1mg/ml), is already available for Patients. A new&#xD;
      ophthalmic gel, preservative-free formulation has been developed. This new formulation has&#xD;
      been tested in pre-clinical animal studies and in a clinical trial. The new formulation&#xD;
      contains Xanthan gum, a high molecular mass polysaccharide approved by the FDA in 1969 for&#xD;
      food products. It is used in the product as viscosity enhancer and to give to the product&#xD;
      pseudo-plastic characteristics and prolonged ocular retention time.&#xD;
&#xD;
      The purpose of this trial is to show that the administration of a reduced dose of NETILDEX ™&#xD;
      gel 2 times a day starting on the day of cataract extraction by means of phaco-emulsification&#xD;
      and administered until 14 days after surgery is sufficient to obtain a non-inferior efficacy&#xD;
      of the NETILDEX ™ eye drops solution administered 4 times a day for the same period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cataract is an ophthalmic disease that usually affects the elderly population. Therapy is&#xD;
      surgical and during the past decades, improvements in surgical techniques and instruments&#xD;
      have dramatically increased the number of cataract extractions performed.&#xD;
&#xD;
      With improvements in surgical techniques, Patients' expectations have risen proportionally;&#xD;
      however, differences in surgical technique impact the severity of surgical trauma and&#xD;
      post-operative recovery. Cataract surgery with phaco-emulsification is now the most&#xD;
      frequently performed intraocular surgical procedure in the developed world.&#xD;
&#xD;
      The amount of post-operative ocular pain and inflammation plays a significant role in the&#xD;
      Patient's perception of the surgical success.&#xD;
&#xD;
      Ocular inflammation, commonly observed after cataract surgery, is associated with a breakdown&#xD;
      of the blood-aqueous barrier (BAB) as a result of surgical trauma-induced prostaglandin&#xD;
      production.&#xD;
&#xD;
      Anterior chamber ocular inflammation, clinically assessed as anterior chamber cell counts and&#xD;
      flare, is also common following cataract surgery. However, post-surgery inflammation is&#xD;
      frequently viewed as an acceptable risk that is largely outweighed by the numerous benefits&#xD;
      of cataract surgery.&#xD;
&#xD;
      Advanced surgical techniques including phaco-emulsification, capsulorhexis, small clear&#xD;
      corneal incisions, improved visco-elastics and foldable implants have helped to optimize&#xD;
      post-surgery results and reduce surgical trauma. However, post-surgery inflammation may still&#xD;
      occur and can lead to complications such as corneal edema, intra-ocular pressure (IOP)&#xD;
      spikes, posterior capsule opacification and cystoid macular edema (CME).&#xD;
&#xD;
      The management of post-surgery inflammation is essential, both to ensure rapid recovery&#xD;
      following surgery, and to prevent or decrease the potential for long-term complications, such&#xD;
      as cystoid macular edema.&#xD;
&#xD;
      Several ophthalmic products have been studied for the management of post-surgery ocular&#xD;
      inflammation and pain following cataract surgery. The two main treatments for ocular&#xD;
      inflammation are topical corticosteroids or non-steroidal anti-inflammatory (NSAID) drugs.&#xD;
&#xD;
      Bromfenac is a potent inhibitor of the COX-2 enzyme and a highly lipophilic molecule that&#xD;
      rapidly penetrates to produce early and sustained drug levels in all ocular tissues. Studies&#xD;
      have shown that Bromfenac ophthalmic solution has equivalent efficacy to the other topical&#xD;
      NSAIDs in reducing post-operative inflammation and controlling pain.&#xD;
&#xD;
      In order to decrease both intra-surgical and post-operative inflammation, it is now becoming&#xD;
      commonplace to extend ophthalmic NSAID dosing to pre-operative use as well to reduce&#xD;
      inflammation and minimize the risk of post-surgery complications in particular to prevent&#xD;
      post-surgery cystoid macular edema.&#xD;
&#xD;
      Corticosteroids are considered the gold standard for the treatment of ocular inflammation,&#xD;
      they are routinely used to control post-surgery ocular inflammation. The most commonly used&#xD;
      route of administration of corticosteroid agents is the topical instillation as eye drops&#xD;
      formulation. Steroids can be used as an additional prophylactic treatment in high-risk cases.&#xD;
&#xD;
      After topical administration of Dexamethasone, the concentration in the anterior chamber&#xD;
      increases and declines within hours, necessitating frequent daily instillations of eye drops&#xD;
      for several weeks. This might be associated with compliance issues, particularly in elderly&#xD;
      Patients or in individuals with disabilities. A pharmaceutical formulation allowing for a&#xD;
      less frequent administration could therefore be an attractive alternative.&#xD;
&#xD;
      Increase in intra-ocular pressure (IOP) is a concern after the use of corticosteroids,&#xD;
      irrespective of the route of administration. Repeated use of topical steroids has been shown&#xD;
      to induce reversible elevations in IOP, especially in eyes with glaucoma.&#xD;
&#xD;
      Although most of the Patients develop an increase in IOP after 3-6 weeks of treatment with&#xD;
      topical steroids, some elevation of IOP can be found as early as the first or second week&#xD;
      after initiation of topical instillation of steroids.&#xD;
&#xD;
      NETILDEX™ eye drops solution, containing Netilmicin Sulfate 4.55 mg (3mg/ml) and&#xD;
      Dexamethasone Disodium Phosphate 1.32 mg (1mg/ml), is already available for Patients. A new&#xD;
      ophthalmic gel, preservative-free formulation has been developed. This new formulation has&#xD;
      been tested in pre-clinical animal studies and in a clinical trial. The new formulation&#xD;
      contains Xanthan gum, a high molecular mass polysaccharide approved by the FDA in 1969 for&#xD;
      food products and it is used in the product as viscosity enhancer and to give to the product&#xD;
      pseudo-plastic characteristics and prolonged ocular retention time. Its usability in&#xD;
      ophthalmic preparations is well known and another products containing Xanthan gum is&#xD;
      currently available in the market (Timolol GFS, Falcon Pharmaceuticals, USA).&#xD;
&#xD;
      The penetration in the target tissue of Netilmicin and Dexamethasone contained in NETILDEX ™&#xD;
      eye drops and NETILDEX™ ophthalmic gel has been studied in a pre-clinical study in rabbits,&#xD;
      which results suggest that the ophthalmic gel formulation increases the tissue&#xD;
      bioavailability of both active principles.&#xD;
&#xD;
      A clinical study has been conducted in 63 healthy volunteers (21 per group) to establish the&#xD;
      safety and ocular tolerability of NETILDEX ™ ophthalmic gel, in comparison with placebo and&#xD;
      eye drop solution, administered q.i.d. (1 drop) over a period of 14 days . Both formulations&#xD;
      were tolerated as placebo. A statistically significant difference between placebo and&#xD;
      Dexamethasone/Netilmicin was observed, as expected, for intra-ocular pressure (IOP) values,&#xD;
      however in none of the cases the IOP rising was clinically relevant.&#xD;
&#xD;
      The purpose of this trial is to show that the administration of a reduced dose of NETILDEX ™&#xD;
      gel 2 times a day starting on the day of cataract extraction by means of phaco-emulsification&#xD;
      and administered until 14 days after surgery is sufficient to obtain a non-inferior efficacy&#xD;
      of the NETILDEX ™ eye drops solution administered 4 times a day for the same period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 15, 2017</start_date>
  <completion_date type="Actual">December 30, 2018</completion_date>
  <primary_completion_date type="Actual">December 1, 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Two treatment arms, test group versus active-comparator (control) group, treated in parallel.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>All daily study products will be manufactured in indistinguishable single dose plastic vials, labeled in accordance with hour of administration. In accordance with the double-blind design of the study, daily treatment for patients randomized to group A (NETILDEX™ ophthalmic gel), will be of 2 doses of active treatment and 2 doses of indistinguishable placebo. For blinding purposes, Group B (NETILDEX™ eye drops solution) medications labels will consist in an aluminum envelope for each dose of the daily treatment, containing indistinguishable plastic vials of NETILDEX™ eye drops solution. Tertiary packaging (patient's treatment supply) will be a carton box appropriately labeled, containing 16 secondary packages (aluminum envelopes - each envelope containing 5 vials for each treatment time dose), containing enough plastic vials to allow the patient to complete the whole study treatment.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Measurement of inflammation conditions in the anterior ocular chamber after cataract extraction through Slit Lamp and Bio-microscopy.</measure>
    <time_frame>Throughout study completion, approximately 9 weeks.</time_frame>
    <description>The measurement aims to demonstrate the efficacy of a reduced frequency of administration of NETILDEX™ ophthalmic gel, administered twice daily (b.i.d.), in comparison with NETILDEX™ eye drops solution, administered four times a day (q.i.d.), in the prevention of post-surgery inflammation after cataract extraction by means of phaco-emulsification.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluation of antibiotic efficacy based on the presence of detected microbial infections (positive ocular swabs and anti-biogram results, if any).</measure>
    <time_frame>Within 24 hours after cataract surgery.</time_frame>
    <description>The anti-biogram should be performed according to standard procedure at investigational sites, but including at least the test with Netilmicin and Cefuroxime.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of a potential variation in the intra-ocular pressure related to the use of the gel formulation compared to the eye-drops formulation, through its measurement before and after treatment.</measure>
    <time_frame>Throughout study completion, approximately 9 weeks.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of clinical signs and symptoms of ocular inflammation (other than flare and cellularity) through standard scoring systems.</measure>
    <time_frame>Throughout study completion, approximately 9 weeks.</time_frame>
    <description>In particular, attention will be focused on the evaluation in treated Patients of: degree of conjunctival hyperemia; lid/corneal edema; ocular discomfort.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of visual acuity through standard measurement systems.</measure>
    <time_frame>Throughout study completion, approximately 9 weeks.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the global tolerability of NETILDEX™ ophthalmic gel in treated Patients (by the Investigator), through a standard questionnaire.</measure>
    <time_frame>Within 2 weeks after cataract surgery.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the safety of NETILDEX™ ophthalmic gel through the collection and evaluation of adverse events.</measure>
    <time_frame>Throughout study completion, approximately 9 weeks.</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">180</enrollment>
  <condition>Cataract Extraction</condition>
  <condition>Cataract</condition>
  <arm_group>
    <arm_group_label>NETILDEX™ ophthalmic gel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 drop of NETILDEX™ (Netilmicin Sulfate 3mg/ml / Dexamethasone Disodium Phosphate 1mg/ml) ophthalmic gel immediately after the surgery then 1 drop twice daily (b.i.d.) from Day 1 until Day 14 after surgery + 1 drop of XANTERGEL™ ophthalmic gel twice daily (b.i.d.) from Day 1 until Day 14 after surgery.&#xD;
Bromfenac 0.9 mg/ml 1 drop twice daily (b.i.d.) for 3 days before cataract surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NETILDEX™ eye drops solution</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1 drop of NETILDEX™ (Netilmicin Sulfate 3mg/ml / Dexamethasone Disodium Phosphate 1mg/ml) eye drops solution immediately after the surgery then 1 drop four times a day (q.i.d.) from Day 1 until Day 14 after surgery.&#xD;
Bromfenac 0.9 mg/ml 1 drop twice daily (b.i.d.) for 3 days before cataract surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NETILDEX™ ophthalmic gel</intervention_name>
    <description>1 drop of NETILDEX™ (Netilmicin Sulfate 3mg/ml / Dexamethasone Disodium Phosphate 1mg/ml) ophthalmic gel immediately after the surgery then 1 drop twice daily (b.i.d.) from Day 1 until Day 14 after surgery + 1 drop of XANTERGEL™ ophthalmic gel twice daily (b.i.d.) from Day 1 until Day 14 after surgery.&#xD;
Bromfenac 0.9 mg/ml 1 drop twice daily (b.i.d.) for 3 days before cataract surgery.</description>
    <arm_group_label>NETILDEX™ ophthalmic gel</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NETILDEX™ eye drops solution</intervention_name>
    <description>1 drop of NETILDEX™ (Netilmicin Sulfate 3mg/ml / Dexamethasone Disodium Phosphate 1mg/ml) eye drops solution immediately after the surgery then 1 drop four times a day (q.i.d.) from Day 1 until Day 14 after surgery.&#xD;
Bromfenac 0.9 mg/ml 1 drop twice daily (b.i.d.) for 3 days before cataract surgery.</description>
    <arm_group_label>NETILDEX™ eye drops solution</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female Patients&#xD;
&#xD;
          2. Patients aged ≥ 40 years old&#xD;
&#xD;
          3. Patients undergoing cataract extraction surgery through phaco-emulsification and&#xD;
             intra-ocular lens implantation&#xD;
&#xD;
          4. Patients with grade 2 or 3 according to LOCS III system for grading age-related&#xD;
             cataract&#xD;
&#xD;
          5. Patients with transparent cornea (endothelial count in the limits for age but not&#xD;
             lower than 1200 cells/mm2)&#xD;
&#xD;
          6. Patients understanding the nature of the study and providing their informed consent to&#xD;
             participation&#xD;
&#xD;
          7. Patients willing and able to attend the visits and procedures foreseen by study&#xD;
             protocol&#xD;
&#xD;
          8. Patients with negative Amsler Test at enrolment visit (V1)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with medical history of ocular inflammation diseases, Herpes infections,&#xD;
             iritis, uveitis or Sjogren's syndrome&#xD;
&#xD;
          -  Patients who have been treated for external ocular infections within a month before&#xD;
             the study enrolment (V1)&#xD;
&#xD;
          -  Patients with cellularity in the anterior ocular chamber ≥ grade 2 (16-25 cells /&#xD;
             field 1x1 mm)&#xD;
&#xD;
          -  Patients with flare in the anterior ocular chamber ≥ grade 2 (moderate)&#xD;
&#xD;
          -  Patients with at least one of the following concomitant ocular diseases: ocular&#xD;
             infections, uveitis, iritis, iridociclitis, glaucoma, diabetic retinopathy, diabetes,&#xD;
             maculopathy, shallow anterior chamber (based on Investigator's judgment)&#xD;
&#xD;
          -  Patients with PEX Syndrome (Pseudo-exfoliation syndrome)&#xD;
&#xD;
          -  Patients with poor mydriasis, basing on Investigator's judgment&#xD;
&#xD;
          -  Patients with intra-ocular pressure &gt; 24 mmHg&#xD;
&#xD;
          -  Patients who have undergone surgery in the eye involved in the cataract extraction&#xD;
             within the 12 months before the study enrolment (V1)&#xD;
&#xD;
          -  Patients who have received corneal laser treatment in the eye involved in the cataract&#xD;
             extraction within the 6 months before the study enrolment (V1)&#xD;
&#xD;
          -  Patients with known or suspected allergy or hypersensitivity to ophthalmic&#xD;
             preservatives, phenylacetic acid derivatives, aminoglycosides, Bromfenac, other&#xD;
             NSAIDs, steroids&#xD;
&#xD;
          -  Patients with traumatic cataract condition&#xD;
&#xD;
          -  Patients who have been treated or are under treatment with alpha-blocking agents for&#xD;
             more than 3 months before the study enrolment (V1)&#xD;
&#xD;
          -  Patients who have received treatment with anti-histamines, decongestants,&#xD;
             anti-inflammatory steroidal or non-steroidal (NSAID) drugs within the 15 days before&#xD;
             the study enrolment (V1). Bromfenac, only, will be allowed for 3 days before cataract&#xD;
             surgery&#xD;
&#xD;
          -  Patients who are participating or have participated in other clinical studies within&#xD;
             the 30 days before the study enrolment (V1)&#xD;
&#xD;
          -  Patients receiving any ocular treatment, with the exception of artificial tears&#xD;
&#xD;
          -  Female Patients who are pregnant or breast-feeding or who wish to become pregnant&#xD;
             during the period of the clinical study and for three months later&#xD;
&#xD;
          -  Female Patients of childbearing age (less than 24 months after the last menstrual&#xD;
             cycle) who do not use adequate contraception *&#xD;
&#xD;
          -  Monocle Patients&#xD;
&#xD;
          -  Patients with epiretinal membrane as per OCT test at enrolment visit (V1)&#xD;
&#xD;
               -  Methods at low risk of contraceptive failure (less than 1% per year) when used&#xD;
                  consistently, including: combined (estrogen and progestogen containing) hormonal&#xD;
                  contraception associated with inhibition of ovulation (oral, intravaginal,&#xD;
                  transdermal), progestogen-only hormonal contraception associated with inhibition&#xD;
                  of ovulation (oral, injectable, implantable), some intra-uterine devices,&#xD;
                  abstinence or vasectomized partner. Contraception should be maintained until&#xD;
                  treatment discontinuation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Aldo Caporossi, MD, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Policlinico Universitario A. Gemelli</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Klinikum Ernst von Bergmann Ophthalmologie</name>
      <address>
        <city>Potsdam</city>
        <zip>14467</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Augenklinik und Poliklinik Ophthalmologie</name>
      <address>
        <city>Wurzburg</city>
        <zip>87080</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero-Universitaria Careggi</name>
      <address>
        <city>Firenze</city>
        <zip>50134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Fatebenefratelli e Oftalmico</name>
      <address>
        <city>Milano</city>
        <zip>20121</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico Universitario A. Gemelli</name>
      <address>
        <city>Roma</city>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrul Medical Unirea</name>
      <address>
        <city>Bucuresti</city>
        <zip>010576</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spitalul Universitar de Urgenta Bucuresti</name>
      <address>
        <city>Bucuresti</city>
        <zip>050098</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Italy</country>
    <country>Romania</country>
  </location_countries>
  <reference>
    <citation>Harrer A, Gerstmeyer K, Hirnschall N, Pesudovs K, Lundstrom M, Findl O. Impact of bilateral cataract surgery on vision-related activity limitations. J Cataract Refract Surg. 2013 May;39(5):680-5. doi: 10.1016/j.jcrs.2012.11.028. Epub 2013 Mar 25.</citation>
    <PMID>23535380</PMID>
  </reference>
  <reference>
    <citation>Porela-Tiihonen S, Kaarniranta K, Kokki H. Postoperative pain after cataract surgery. J Cataract Refract Surg. 2013 May;39(5):789-98. doi: 10.1016/j.jcrs.2013.03.012.</citation>
    <PMID>23608571</PMID>
  </reference>
  <reference>
    <citation>Monnet D, Tepenier L, Brezin AP. Objective assessment of inflammation after cataract surgery: comparison of 3 similar intraocular lens models. J Cataract Refract Surg. 2009 Apr;35(4):677-81. doi: 10.1016/j.jcrs.2008.12.021.</citation>
    <PMID>19304088</PMID>
  </reference>
  <reference>
    <citation>Goodman DF, Stark WJ, Gottsch JD. Complications of cataract extraction with intraocular lens implantation. Ophthalmic Surg. 1989 Feb;20(2):132-40.</citation>
    <PMID>2648237</PMID>
  </reference>
  <reference>
    <citation>Perry HD, Donnenfeld ED. An update on the use of ophthalmic ketorolac tromethamine 0.4%. Expert Opin Pharmacother. 2006 Jan;7(1):99-107. doi: 10.1517/14656566.7.1.99.</citation>
    <PMID>16370927</PMID>
  </reference>
  <reference>
    <citation>Sandoval HP, Fernandez de Castro LE, Vroman DT, Solomon KD. A review of the use of ketorolac tromethamine 0.4% in the treatment of post-surgical inflammation following cataract and refractive surgery. Clin Ophthalmol. 2007 Dec;1(4):367-71.</citation>
    <PMID>19668513</PMID>
  </reference>
  <reference>
    <citation>Alio JL, Sayans JA, Chipont E. Laser flare-cell measurement of inflammation after uneventful extracapsular cataract extraction and intraocular lens implantation. J Cataract Refract Surg. 1996;22 Suppl 1:775-9. doi: 10.1016/s0886-3350(96)80161-1.</citation>
    <PMID>9279671</PMID>
  </reference>
  <reference>
    <citation>Pande MV, Spalton DJ, Kerr-Muir MG, Marshall J. Postoperative inflammatory response to phacoemulsification and extracapsular cataract surgery: aqueous flare and cells. J Cataract Refract Surg. 1996;22 Suppl 1:770-4. doi: 10.1016/s0886-3350(96)80160-x.</citation>
    <PMID>9279670</PMID>
  </reference>
  <reference>
    <citation>Laurell CG, Zetterstrom C, Philipson B, Syren-Nordqvist S. Randomized study of the blood-aqueous barrier reaction after phacoemulsification and extracapsular cataract extraction. Acta Ophthalmol Scand. 1998 Oct;76(5):573-8. doi: 10.1034/j.1600-0420.1998.760512.x.</citation>
    <PMID>9826042</PMID>
  </reference>
  <reference>
    <citation>El-Harazi SM, Feldman RM. Control of intra-ocular inflammation associated with cataract surgery. Curr Opin Ophthalmol. 2001 Feb;12(1):4-8. doi: 10.1097/00055735-200102000-00002.</citation>
    <PMID>11150074</PMID>
  </reference>
  <reference>
    <citation>Rotsos TG, Moschos MM. Cystoid macular edema. Clin Ophthalmol. 2008 Dec;2(4):919-30. doi: 10.2147/opth.s4033.</citation>
    <PMID>19668445</PMID>
  </reference>
  <reference>
    <citation>Gulkilik G, Kocabora S, Taskapili M, Engin G. Cystoid macular edema after phacoemulsification: risk factors and effect on visual acuity. Can J Ophthalmol. 2006 Dec;41(6):699-703. doi: 10.3129/i06-062.</citation>
    <PMID>17224950</PMID>
  </reference>
  <reference>
    <citation>Cho H, Wolf KJ, Wolf EJ. Management of ocular inflammation and pain following cataract surgery: focus on bromfenac ophthalmic solution. Clin Ophthalmol. 2009;3:199-210. doi: 10.2147/opth.s4806. Epub 2009 Jun 2.</citation>
    <PMID>19668566</PMID>
  </reference>
  <reference>
    <citation>Rajpal RK, Ross B, Rajpal SD, Hoang K. Bromfenac ophthalmic solution for the treatment of postoperative ocular pain and inflammation: safety, efficacy, and patient adherence. Patient Prefer Adherence. 2014 Jun 25;8:925-31. doi: 10.2147/PPA.S46667. eCollection 2014.</citation>
    <PMID>25028541</PMID>
  </reference>
  <reference>
    <citation>Korenfeld MS, Silverstein SM, Cooke DL, Vogel R, Crockett RS; Difluprednate Ophthalmic Emulsion 0.05% (Durezol) Study Group. Difluprednate ophthalmic emulsion 0.05% for postoperative inflammation and pain. J Cataract Refract Surg. 2009 Jan;35(1):26-34. doi: 10.1016/j.jcrs.2008.09.024.</citation>
    <PMID>19101421</PMID>
  </reference>
  <reference>
    <citation>Lorenz K, Dick B, Jehkul A, Auffahrt GU. Inflammatory response after phacoemulsification treated with 0.5% prednisolone acetate or vehicle. Graefes Arch Clin Exp Ophthalmol. 2008 Nov;246(11):1617-22. doi: 10.1007/s00417-008-0908-2. Epub 2008 Aug 26.</citation>
    <PMID>18726610</PMID>
  </reference>
  <reference>
    <citation>Comstock TL, Paterno MR, Singh A, Erb T, Davis E. Safety and efficacy of loteprednol etabonate ophthalmic ointment 0.5% for the treatment of inflammation and pain following cataract surgery. Clin Ophthalmol. 2011;5:177-86. doi: 10.2147/OPTH.S16832. Epub 2011 Feb 10.</citation>
    <PMID>21383946</PMID>
  </reference>
  <reference>
    <citation>McGhee CN, Dean S, Danesh-Meyer H. Locally administered ocular corticosteroids: benefits and risks. Drug Saf. 2002;25(1):33-55. doi: 10.2165/00002018-200225010-00004.</citation>
    <PMID>11820911</PMID>
  </reference>
  <reference>
    <citation>Sanders DR, Kraff M. Steroidal and nonsteroidal anti-inflammatory agents. Effect on postsurgical inflammation and blood-aqueous humor barrier breakdown. Arch Ophthalmol. 1984 Oct;102(10):1453-6. doi: 10.1001/archopht.1984.01040031173012.</citation>
    <PMID>6385931</PMID>
  </reference>
  <reference>
    <citation>Corbett MC, Hingorani M, Boulton JE, Shilling JS. Subconjunctival betamethasone is of benefit after cataract surgery. Eye (Lond). 1993;7 ( Pt 6):744-8. doi: 10.1038/eye.1993.173.</citation>
    <PMID>8119423</PMID>
  </reference>
  <reference>
    <citation>Watson D, Noble MJ, Dutton GN, Midgley JM, Healey TM. Penetration of topically applied dexamethasone alcohol into human aqueous humor. Arch Ophthalmol. 1988 May;106(5):686-7. doi: 10.1001/archopht.1988.01060130748037.</citation>
    <PMID>3358736</PMID>
  </reference>
  <reference>
    <citation>Winfield AJ, Jessiman D, Williams A, Esakowitz L. A study of the causes of non-compliance by patients prescribed eyedrops. Br J Ophthalmol. 1990 Aug;74(8):477-80. doi: 10.1136/bjo.74.8.477.</citation>
    <PMID>2390523</PMID>
  </reference>
  <reference>
    <citation>ARMALY MF. EFFECT OF CORTICOSTEROIDS ON INTRAOCULAR PRESSURE AND FLUID DYNAMICS. I. THE EFFECT OF DEXAMETHASONE IN THE NORMAL EYE. Arch Ophthalmol. 1963 Oct;70:482-91. doi: 10.1001/archopht.1963.00960050484010. No abstract available.</citation>
    <PMID>14078870</PMID>
  </reference>
  <reference>
    <citation>BECKER B, MILLS DW. CORTICOSTEROIDS AND INTRAOCULAR PRESSURE. Arch Ophthalmol. 1963 Oct;70:500-7. doi: 10.1001/archopht.1963.00960050502012. No abstract available.</citation>
    <PMID>14078872</PMID>
  </reference>
  <reference>
    <citation>Bartlett JD, Woolley TW, Adams CM. Identification of high intraocular pressure responders to topical ophthalmic corticosteroids. J Ocul Pharmacol. 1993 Spring;9(1):35-45. doi: 10.1089/jop.1993.9.35.</citation>
    <PMID>8463731</PMID>
  </reference>
  <reference>
    <citation>Barry P, Cordovés L, Gardner S. ESCRS Guidelines for Prevention and Treatment of Endophthalmitis Following Cataract Surgery: Data, Dilemmas and Conclusions. The European Society for Cataract &amp; Refractive Surgeons 2013</citation>
  </reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>November 22, 2016</study_first_submitted>
  <study_first_submitted_qc>November 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 25, 2016</study_first_posted>
  <last_update_submitted>January 10, 2019</last_update_submitted>
  <last_update_submitted_qc>January 10, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 14, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Steroid/antibiotic associated treatment</keyword>
  <keyword>Phaco-emulsification</keyword>
  <keyword>Cataract extraction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cataract</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ophthalmic Solutions</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>June 4, 2020</submitted>
    <submission_canceled>June 5, 2020</submission_canceled>
    <submitted>June 5, 2020</submitted>
    <submission_canceled>June 6, 2020</submission_canceled>
    <submitted>June 6, 2020</submitted>
    <submission_canceled>June 8, 2020</submission_canceled>
    <submitted>June 8, 2020</submitted>
    <returned>June 25, 2020</returned>
    <submitted>June 26, 2020</submitted>
    <submission_canceled>June 29, 2020</submission_canceled>
    <submitted>June 29, 2020</submitted>
    <submission_canceled>June 30, 2020</submission_canceled>
    <submitted>June 30, 2020</submitted>
    <returned>July 15, 2020</returned>
    <submitted>October 20, 2020</submitted>
    <returned>November 12, 2020</returned>
    <submitted>March 16, 2021</submitted>
    <returned>April 9, 2021</returned>
    <submitted>December 22, 2022</submitted>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02973880
org study id: 044-SI
secondary id: 2016-002138-63
nct id: NCT02973880
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Cataract is an ophthalmic disease that usually affects the elderly population. Cataract
      surgery with phaco-emulsification is now the most frequently performed intraocular surgical
      procedure in the developed world. However, differences in surgical technique impact the
      severity of surgical trauma and post-operative recovery. The amount of post-operative ocular
      pain and inflammation plays a significant role in the Patient's perception of the surgical
      success.

      Several ophthalmic products have been studied in the management of post-surgery ocular
      inflammation and pain following cataract surgery. Corticosteroids are considered the gold
      standard for the treatment of ocular inflammation, and their most commonly used route of
      administration is the topical instillation as eye drops formulation.

      After topical administration of Dexamethasone, the concentration in the anterior chamber
      increases and declines within hours, necessitating frequent daily instillations of eye drops
      for several weeks. This might be associated with compliance issues, particularly in elderly
      Patients or in individuals with disabilities. A pharmaceutical formulation allowing for a
      less frequent administration could therefore be an attractive alternative.

      NETILDEX™ eye drops solution, containing Netilmicin Sulfate 4.55 mg (3mg/ml) and
      Dexamethasone Disodium Phosphate 1.32 mg (1mg/ml), is already available for Patients. A new
      ophthalmic gel, preservative-free formulation has been developed. This new formulation has
      been tested in pre-clinical animal studies and in a clinical trial. The new formulation
      contains Xanthan gum, a high molecular mass polysaccharide approved by the FDA in 1969 for
      food products. It is used in the product as viscosity enhancer and to give to the product
      pseudo-plastic characteristics and prolonged ocular retention time.

      The purpose of this trial is to show that the administration of a reduced dose of NETILDEX ™
      gel 2 times a day starting on the day of cataract extraction by means of phaco-emulsification
      and administered until 14 days after surgery is sufficient to obtain a non-inferior efficacy
      of the NETILDEX ™ eye drops solution administered 4 times a day for the same period.
Cataract is an ophthalmic disease that usually affects the elderly population. Therapy is
      surgical and during the past decades, improvements in surgical techniques and instruments
      have dramatically increased the number of cataract extractions performed.

      With improvements in surgical techniques, Patients' expectations have risen proportionally;
      however, differences in surgical technique impact the severity of surgical trauma and
      post-operative recovery. Cataract surgery with phaco-emulsification is now the most
      frequently performed intraocular surgical procedure in the developed world.

      The amount of post-operative ocular pain and inflammation plays a significant role in the
      Patient's perception of the surgical success.

      Ocular inflammation, commonly observed after cataract surgery, is associated with a breakdown
      of the blood-aqueous barrier (BAB) as a result of surgical trauma-induced prostaglandin
      production.

      Anterior chamber ocular inflammation, clinically assessed as anterior chamber cell counts and
      flare, is also common following cataract surgery. However, post-surgery inflammation is
      frequently viewed as an acceptable risk that is largely outweighed by the numerous benefits
      of cataract surgery.

      Advanced surgical techniques including phaco-emulsification, capsulorhexis, small clear
      corneal incisions, improved visco-elastics and foldable implants have helped to optimize
      post-surgery results and reduce surgical trauma. However, post-surgery inflammation may still
      occur and can lead to complications such as corneal edema, intra-ocular pressure (IOP)
      spikes, posterior capsule opacification and cystoid macular edema (CME).

      The management of post-surgery inflammation is essential, both to ensure rapid recovery
      following surgery, and to prevent or decrease the potential for long-term complications, such
      as cystoid macular edema.

      Several ophthalmic products have been studied for the management of post-surgery ocular
      inflammation and pain following cataract surgery. The two main treatments for ocular
      inflammation are topical corticosteroids or non-steroidal anti-inflammatory (NSAID) drugs.

      Bromfenac is a potent inhibitor of the COX-2 enzyme and a highly lipophilic molecule that
      rapidly penetrates to produce early and sustained drug levels in all ocular tissues. Studies
      have shown that Bromfenac ophthalmic solution has equivalent efficacy to the other topical
      NSAIDs in reducing post-operative inflammation and controlling pain.

      In order to decrease both intra-surgical and post-operative inflammation, it is now becoming
      commonplace to extend ophthalmic NSAID dosing to pre-operative use as well to reduce
      inflammation and minimize the risk of post-surgery complications in particular to prevent
      post-surgery cystoid macular edema.

      Corticosteroids are considered the gold standard for the treatment of ocular inflammation,
      they are routinely used to control post-surgery ocular inflammation. The most commonly used
      route of administration of corticosteroid agents is the topical instillation as eye drops
      formulation. Steroids can be used as an additional prophylactic treatment in high-risk cases.

      After topical administration of Dexamethasone, the concentration in the anterior chamber
      increases and declines within hours, necessitating frequent daily instillations of eye drops
      for several weeks. This might be associated with compliance issues, particularly in elderly
      Patients or in individuals with disabilities. A pharmaceutical formulation allowing for a
      less frequent administration could therefore be an attractive alternative.

      Increase in intra-ocular pressure (IOP) is a concern after the use of corticosteroids,
      irrespective of the route of administration. Repeated use of topical steroids has been shown
      to induce reversible elevations in IOP, especially in eyes with glaucoma.

      Although most of the Patients develop an increase in IOP after 3-6 weeks of treatment with
      topical steroids, some elevation of IOP can be found as early as the first or second week
      after initiation of topical instillation of steroids.

      NETILDEX™ eye drops solution, containing Netilmicin Sulfate 4.55 mg (3mg/ml) and
      Dexamethasone Disodium Phosphate 1.32 mg (1mg/ml), is already available for Patients. A new
      ophthalmic gel, preservative-free formulation has been developed. This new formulation has
      been tested in pre-clinical animal studies and in a clinical trial. The new formulation
      contains Xanthan gum, a high molecular mass polysaccharide approved by the FDA in 1969 for
      food products and it is used in the product as viscosity enhancer and to give to the product
      pseudo-plastic characteristics and prolonged ocular retention time. Its usability in
      ophthalmic preparations is well known and another products containing Xanthan gum is
      currently available in the market (Timolol GFS, Falcon Pharmaceuticals, USA).

      The penetration in the target tissue of Netilmicin and Dexamethasone contained in NETILDEX ™
      eye drops and NETILDEX™ ophthalmic gel has been studied in a pre-clinical study in rabbits,
      which results suggest that the ophthalmic gel formulation increases the tissue
      bioavailability of both active principles.

      A clinical study has been conducted in 63 healthy volunteers (21 per group) to establish the
      safety and ocular tolerability of NETILDEX ™ ophthalmic gel, in comparison with placebo and
      eye drop solution, administered q.i.d. (1 drop) over a period of 14 days . Both formulations
      were tolerated as placebo. A statistically significant difference between placebo and
      Dexamethasone/Netilmicin was observed, as expected, for intra-ocular pressure (IOP) values,
      however in none of the cases the IOP rising was clinically relevant.

      The purpose of this trial is to show that the administration of a reduced dose of NETILDEX ™
      gel 2 times a day starting on the day of cataract extraction by means of phaco-emulsification
      and administered until 14 days after surgery is sufficient to obtain a non-inferior efficacy
      of the NETILDEX ™ eye drops solution administered 4 times a day for the same period.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Two treatment arms, test group versus active-comparator (control) group, treated in parallel.
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: All daily study products will be manufactured in indistinguishable single dose plastic vials, labeled in accordance with hour of administration. In accordance with the double-blind design of the study, daily treatment for patients randomized to group A (NETILDEX™ ophthalmic gel), will be of 2 doses of active treatment and 2 doses of indistinguishable placebo. For blinding purposes, Group B (NETILDEX™ eye drops solution) medications labels will consist in an aluminum envelope for each dose of the daily treatment, containing indistinguishable plastic vials of NETILDEX™ eye drops solution. Tertiary packaging (patient's treatment supply) will be a carton box appropriately labeled, containing 16 secondary packages (aluminum envelopes - each envelope containing 5 vials for each treatment time dose), containing enough plastic vials to allow the patient to complete the whole study treatment.
measure: Measurement of inflammation conditions in the anterior ocular chamber after cataract extraction through Slit Lamp and Bio-microscopy.
time frame: Throughout study completion, approximately 9 weeks.
description: The measurement aims to demonstrate the efficacy of a reduced frequency of administration of NETILDEX™ ophthalmic gel, administered twice daily (b.i.d.), in comparison with NETILDEX™ eye drops solution, administered four times a day (q.i.d.), in the prevention of post-surgery inflammation after cataract extraction by means of phaco-emulsification.
measure: Evaluation of antibiotic efficacy based on the presence of detected microbial infections (positive ocular swabs and anti-biogram results, if any).
time frame: Within 24 hours after cataract surgery.
description: The anti-biogram should be performed according to standard procedure at investigational sites, but including at least the test with Netilmicin and Cefuroxime.
measure: Assessment of a potential variation in the intra-ocular pressure related to the use of the gel formulation compared to the eye-drops formulation, through its measurement before and after treatment.
time frame: Throughout study completion, approximately 9 weeks.
measure: Evaluation of clinical signs and symptoms of ocular inflammation (other than flare and cellularity) through standard scoring systems.
time frame: Throughout study completion, approximately 9 weeks.
description: In particular, attention will be focused on the evaluation in treated Patients of: degree of conjunctival hyperemia; lid/corneal edema; ocular discomfort.
measure: Evaluation of visual acuity through standard measurement systems.
time frame: Throughout study completion, approximately 9 weeks.
measure: Evaluation of the global tolerability of NETILDEX™ ophthalmic gel in treated Patients (by the Investigator), through a standard questionnaire.
time frame: Within 2 weeks after cataract surgery.
measure: Evaluation of the safety of NETILDEX™ ophthalmic gel through the collection and evaluation of adverse events.
time frame: Throughout study completion, approximately 9 weeks.
arm group label: NETILDEX™ ophthalmic gel
arm group type: Experimental
description: 1 drop of NETILDEX™ (Netilmicin Sulfate 3mg/ml / Dexamethasone Disodium Phosphate 1mg/ml) ophthalmic gel immediately after the surgery then 1 drop twice daily (b.i.d.) from Day 1 until Day 14 after surgery + 1 drop of XANTERGEL™ ophthalmic gel twice daily (b.i.d.) from Day 1 until Day 14 after surgery.
Bromfenac 0.9 mg/ml 1 drop twice daily (b.i.d.) for 3 days before cataract surgery.
arm group label: NETILDEX™ eye drops solution
arm group type: Active Comparator
description: 1 drop of NETILDEX™ (Netilmicin Sulfate 3mg/ml / Dexamethasone Disodium Phosphate 1mg/ml) eye drops solution immediately after the surgery then 1 drop four times a day (q.i.d.) from Day 1 until Day 14 after surgery.
Bromfenac 0.9 mg/ml 1 drop twice daily (b.i.d.) for 3 days before cataract surgery.
intervention type: Drug
intervention name: NETILDEX™ ophthalmic gel
description: 1 drop of NETILDEX™ (Netilmicin Sulfate 3mg/ml / Dexamethasone Disodium Phosphate 1mg/ml) ophthalmic gel immediately after the surgery then 1 drop twice daily (b.i.d.) from Day 1 until Day 14 after surgery + 1 drop of XANTERGEL™ ophthalmic gel twice daily (b.i.d.) from Day 1 until Day 14 after surgery.
Bromfenac 0.9 mg/ml 1 drop twice daily (b.i.d.) for 3 days before cataract surgery.
arm group label: NETILDEX™ ophthalmic gel
intervention type: Drug
intervention name: NETILDEX™ eye drops solution
description: 1 drop of NETILDEX™ (Netilmicin Sulfate 3mg/ml / Dexamethasone Disodium Phosphate 1mg/ml) eye drops solution immediately after the surgery then 1 drop four times a day (q.i.d.) from Day 1 until Day 14 after surgery.
Bromfenac 0.9 mg/ml 1 drop twice daily (b.i.d.) for 3 days before cataract surgery.
arm group label: NETILDEX™ eye drops solution
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Aldo Caporossi, MD, Prof.
role: Principal Investigator
affiliation: Policlinico Universitario A. Gemelli
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
country: Italy
country: Romania
citation: Harrer A, Gerstmeyer K, Hirnschall N, Pesudovs K, Lundstrom M, Findl O. Impact of bilateral cataract surgery on vision-related activity limitations. J Cataract Refract Surg. 2013 May;39(5):680-5. doi: 10.1016/j.jcrs.2012.11.028. Epub 2013 Mar 25.
PMID: 23535380
citation: Porela-Tiihonen S, Kaarniranta K, Kokki H. Postoperative pain after cataract surgery. J Cataract Refract Surg. 2013 May;39(5):789-98. doi: 10.1016/j.jcrs.2013.03.012.
PMID: 23608571
citation: Monnet D, Tepenier L, Brezin AP. Objective assessment of inflammation after cataract surgery: comparison of 3 similar intraocular lens models. J Cataract Refract Surg. 2009 Apr;35(4):677-81. doi: 10.1016/j.jcrs.2008.12.021.
PMID: 19304088
citation: Goodman DF, Stark WJ, Gottsch JD. Complications of cataract extraction with intraocular lens implantation. Ophthalmic Surg. 1989 Feb;20(2):132-40.
PMID: 2648237
citation: Perry HD, Donnenfeld ED. An update on the use of ophthalmic ketorolac tromethamine 0.4%. Expert Opin Pharmacother. 2006 Jan;7(1):99-107. doi: 10.1517/14656566.7.1.99.
PMID: 16370927
citation: Sandoval HP, Fernandez de Castro LE, Vroman DT, Solomon KD. A review of the use of ketorolac tromethamine 0.4% in the treatment of post-surgical inflammation following cataract and refractive surgery. Clin Ophthalmol. 2007 Dec;1(4):367-71.
PMID: 19668513
citation: Alio JL, Sayans JA, Chipont E. Laser flare-cell measurement of inflammation after uneventful extracapsular cataract extraction and intraocular lens implantation. J Cataract Refract Surg. 1996;22 Suppl 1:775-9. doi: 10.1016/s0886-3350(96)80161-1.
PMID: 9279671
citation: Pande MV, Spalton DJ, Kerr-Muir MG, Marshall J. Postoperative inflammatory response to phacoemulsification and extracapsular cataract surgery: aqueous flare and cells. J Cataract Refract Surg. 1996;22 Suppl 1:770-4. doi: 10.1016/s0886-3350(96)80160-x.
PMID: 9279670
citation: Laurell CG, Zetterstrom C, Philipson B, Syren-Nordqvist S. Randomized study of the blood-aqueous barrier reaction after phacoemulsification and extracapsular cataract extraction. Acta Ophthalmol Scand. 1998 Oct;76(5):573-8. doi: 10.1034/j.1600-0420.1998.760512.x.
PMID: 9826042
citation: El-Harazi SM, Feldman RM. Control of intra-ocular inflammation associated with cataract surgery. Curr Opin Ophthalmol. 2001 Feb;12(1):4-8. doi: 10.1097/00055735-200102000-00002.
PMID: 11150074
citation: Rotsos TG, Moschos MM. Cystoid macular edema. Clin Ophthalmol. 2008 Dec;2(4):919-30. doi: 10.2147/opth.s4033.
PMID: 19668445
citation: Gulkilik G, Kocabora S, Taskapili M, Engin G. Cystoid macular edema after phacoemulsification: risk factors and effect on visual acuity. Can J Ophthalmol. 2006 Dec;41(6):699-703. doi: 10.3129/i06-062.
PMID: 17224950
citation: Cho H, Wolf KJ, Wolf EJ. Management of ocular inflammation and pain following cataract surgery: focus on bromfenac ophthalmic solution. Clin Ophthalmol. 2009;3:199-210. doi: 10.2147/opth.s4806. Epub 2009 Jun 2.
PMID: 19668566
citation: Rajpal RK, Ross B, Rajpal SD, Hoang K. Bromfenac ophthalmic solution for the treatment of postoperative ocular pain and inflammation: safety, efficacy, and patient adherence. Patient Prefer Adherence. 2014 Jun 25;8:925-31. doi: 10.2147/PPA.S46667. eCollection 2014.
PMID: 25028541
citation: Korenfeld MS, Silverstein SM, Cooke DL, Vogel R, Crockett RS; Difluprednate Ophthalmic Emulsion 0.05% (Durezol) Study Group. Difluprednate ophthalmic emulsion 0.05% for postoperative inflammation and pain. J Cataract Refract Surg. 2009 Jan;35(1):26-34. doi: 10.1016/j.jcrs.2008.09.024.
PMID: 19101421
citation: Lorenz K, Dick B, Jehkul A, Auffahrt GU. Inflammatory response after phacoemulsification treated with 0.5% prednisolone acetate or vehicle. Graefes Arch Clin Exp Ophthalmol. 2008 Nov;246(11):1617-22. doi: 10.1007/s00417-008-0908-2. Epub 2008 Aug 26.
PMID: 18726610
citation: Comstock TL, Paterno MR, Singh A, Erb T, Davis E. Safety and efficacy of loteprednol etabonate ophthalmic ointment 0.5% for the treatment of inflammation and pain following cataract surgery. Clin Ophthalmol. 2011;5:177-86. doi: 10.2147/OPTH.S16832. Epub 2011 Feb 10.
PMID: 21383946
citation: McGhee CN, Dean S, Danesh-Meyer H. Locally administered ocular corticosteroids: benefits and risks. Drug Saf. 2002;25(1):33-55. doi: 10.2165/00002018-200225010-00004.
PMID: 11820911
citation: Sanders DR, Kraff M. Steroidal and nonsteroidal anti-inflammatory agents. Effect on postsurgical inflammation and blood-aqueous humor barrier breakdown. Arch Ophthalmol. 1984 Oct;102(10):1453-6. doi: 10.1001/archopht.1984.01040031173012.
PMID: 6385931
citation: Corbett MC, Hingorani M, Boulton JE, Shilling JS. Subconjunctival betamethasone is of benefit after cataract surgery. Eye (Lond). 1993;7 ( Pt 6):744-8. doi: 10.1038/eye.1993.173.
PMID: 8119423
citation: Watson D, Noble MJ, Dutton GN, Midgley JM, Healey TM. Penetration of topically applied dexamethasone alcohol into human aqueous humor. Arch Ophthalmol. 1988 May;106(5):686-7. doi: 10.1001/archopht.1988.01060130748037.
PMID: 3358736
citation: Winfield AJ, Jessiman D, Williams A, Esakowitz L. A study of the causes of non-compliance by patients prescribed eyedrops. Br J Ophthalmol. 1990 Aug;74(8):477-80. doi: 10.1136/bjo.74.8.477.
PMID: 2390523
citation: ARMALY MF. EFFECT OF CORTICOSTEROIDS ON INTRAOCULAR PRESSURE AND FLUID DYNAMICS. I. THE EFFECT OF DEXAMETHASONE IN THE NORMAL EYE. Arch Ophthalmol. 1963 Oct;70:482-91. doi: 10.1001/archopht.1963.00960050484010. No abstract available.
PMID: 14078870
citation: BECKER B, MILLS DW. CORTICOSTEROIDS AND INTRAOCULAR PRESSURE. Arch Ophthalmol. 1963 Oct;70:500-7. doi: 10.1001/archopht.1963.00960050502012. No abstract available.
PMID: 14078872
citation: Bartlett JD, Woolley TW, Adams CM. Identification of high intraocular pressure responders to topical ophthalmic corticosteroids. J Ocul Pharmacol. 1993 Spring;9(1):35-45. doi: 10.1089/jop.1993.9.35.
PMID: 8463731
citation: Barry P, Cordovés L, Gardner S. ESCRS Guidelines for Prevention and Treatment of Endophthalmitis Following Cataract Surgery: Data, Dilemmas and Conclusions. The European Society for Cataract & Refractive Surgeons 2013
responsible party type: Sponsor
mesh term: Cataract
mesh term: Ophthalmic Solutions
sharing ipd: No
submitted: June 4, 2020
submission canceled: June 5, 2020
submitted: June 5, 2020
submission canceled: June 6, 2020
submitted: June 6, 2020
submission canceled: June 8, 2020
submitted: June 8, 2020
returned: June 25, 2020
submitted: June 26, 2020
submission canceled: June 29, 2020
submitted: June 29, 2020
submission canceled: June 30, 2020
submitted: June 30, 2020
returned: July 15, 2020
submitted: October 20, 2020
returned: November 12, 2020
submitted: March 16, 2021
returned: April 9, 2021
submitted: December 22, 2022