<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/NCT03798145</url>
  </required_header>
  <id_info>
    <org_study_id>49075</org_study_id>
    <nct_id>NCT03798145</nct_id>
  </id_info>
  <brief_title>Surgical Retinotomy for the Treatment of Glaucoma</brief_title>
  <official_title>Surgical Retinotomy for the Treatment of Glaucoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Stanford University</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>
      Glaucoma is a leading cause of blindness worldwide. It is caused by persistently elevated&#xD;
      intraocular pressure causing progressive visual field loss. While a number of conventional&#xD;
      medical and surgical therapies exist, a significant number of patients fail to respond&#xD;
      resulting in persistently elevated intraocular pressure and eventual blindness. While outflow&#xD;
      from the eye primarily occurs through the front of the eye, there is an often overlooked&#xD;
      pathway to remove fluid that is beneath the retina. Surgical removal of retina to create&#xD;
      paths for outflow (surgical retinotomy) in areas damaged by glaucoma can provide access to&#xD;
      this alternative outflow pathway thereby reducing intraocular pressure and halting the vision&#xD;
      loss.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The goal of this study is to demonstrate that focal surgical retinotomies (holes in the&#xD;
      retina) can result in predictable and lasting reduction in intraocular pressure while&#xD;
      eliminating the risks associated with surgical retinectomy (broad areas of retinal removal).&#xD;
&#xD;
      In the late 1990s and early 2000s, Joussen et al pioneered a technique to lower intraocular&#xD;
      pressure in patients with advanced untreatable glaucoma. All patients had intraocular&#xD;
      pressures on average above 40 that were unresponsive to any available treatments. Forty-four&#xD;
      patients underwent broad areas of retinal removal (retinectomy). All patients exhibited&#xD;
      dramatic reductions in intraocular pressure which were maintained for 5 years (Joussen 2003).&#xD;
      Unfortunately, the technique carried significant risks. 1) a subset of patients had&#xD;
      excessively low intraocular pressure reductions. 2) a subset of patients had secondary&#xD;
      proliferative vitreoretinopathy (a scarring response) that resulting in retinal deatchment.&#xD;
      Despite its incredible effectiveness, these risks made clinicians hesitant to adopt the&#xD;
      technique. Additionally, glaucoma specialists are unable to perform the technical procedures&#xD;
      required creating a chasm between diagnosing physician (glaucoma specialist) and the treating&#xD;
      physician (retina specialist). Finally, surgical microtools tools at the time were still in&#xD;
      their infancy.&#xD;
&#xD;
      The current proposal attempts to make critical modifications to the technique used by Joussen&#xD;
      et al. (2003). First and foremost, we plan to use surgical retinotomies (holes in the retina)&#xD;
      in lieu of a broad surgical retinectomy (broad peripheral retinal removal). This is a&#xD;
      critical difference. Removal of the peripheral retina to the ora serrata carries significant&#xD;
      risk of postoperative proliferative vitreoretinopathy. This is largely due to residual&#xD;
      vitreous which cannot be removed from the far peripheral retina. This residual vitreous&#xD;
      contracts in the postoperative period causing elevation of the retinectomy edges allowing for&#xD;
      retinal detachment. Surgical retinotomies (holes in the retina), that do not involve the&#xD;
      vitreous base are commonly used in retina surgery and do not carry anywhere close to the risk&#xD;
      of retinal detachment that surgical retinectomy carries. As an example, the majority of&#xD;
      retinal detachments are repaired by draining fluid through an iatrogenic surgical retinotomy&#xD;
      (a hole created by the surgeon in the retina). These holes are created in the posterior&#xD;
      retina and yet are virtually always undetectable by the patient. (Of note, a peripheral&#xD;
      retinotomy is even harder to detect). More recently, there has been an upsurge of free-flap&#xD;
      autologous retinal transplantation for macular holes (Grewal 2016) and macular degeneration&#xD;
      (Parolini 2018). In these surgical procedures, an area of peripheral retina is removed and&#xD;
      transplanted to the macula. The site of removal leaves a hole in the retina. In these studies&#xD;
      the rate of redetachment in patients in whom a retinotomy was created is no higher than that&#xD;
      of other standard retina surgeries. It is therefore clear that creation of retinal holes&#xD;
      (retinotomy) is far different in terms of long-term risks than broad retinal removal to the&#xD;
      ora serrata (retinectomy). Additionally, this increase in retina transplantation has been&#xD;
      made possible by the microsurgical surgical tools that are now available. However, in the&#xD;
      case of both the retinal detachment repair and autologous transplantation, the retinotomy&#xD;
      size is not sufficient to induce intraocular pressure lowering effects. We therefore seek to&#xD;
      build upon the original work from Joussen et al (2003) which showed that retina removal can&#xD;
      have dramatic intraocular pressure lowering effects, but seek to use surgical retinotomies&#xD;
      (holes in the retina) to achieve this retinal removal thereby avoiding his surgical&#xD;
      complications while capitalizing on the long-term efficacy. By varying the size and number of&#xD;
      surgical retinotomy, we will be able to provide a normogram for effective prediction of&#xD;
      intraocular pressure lowering effects. By effectively predicting the magnitude of this&#xD;
      surgical procedure, ophthalmologists will have a predictable and reliable method for treating&#xD;
      glaucoma. Furthermore, because a surgical retinotomy does not close, it is predicted to&#xD;
      provide a life-long effect.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">December 2021</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2024</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Intraocular Pressure</measure>
    <time_frame>2 years</time_frame>
    <description>Percentage Reduction in Intraocular Pressure</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Visual Field Progression</measure>
    <time_frame>2 years</time_frame>
    <description>Visual Field Progression on HVF 24-2 or Goldmann Visual Field</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Glaucoma</condition>
  <arm_group>
    <arm_group_label>Surgical Retinotomy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Surgical retinotomy will be constructed in the area of the scotoma.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Surgical Retinotomy</intervention_name>
    <description>Surgical removal of small areas of retinal to increase outflow through the posterior drainage pathway.</description>
    <arm_group_label>Surgical Retinotomy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Glaucoma with reproducible and progressive peripheral field loss Elevated Intraocular&#xD;
        pressure despite topical medications and filtering surgery (trabeculectomy, tube shunts)&#xD;
        Pseudophakia (prior cataract surgery) Greater than 50 years old&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Uveitic Glaucoma Foveal threatening visual field loss (field loss within 5 degrees of&#xD;
        fixation) (i.e. advanced glaucoma) Active ophthalmic infection Monocular (functional vision&#xD;
        in only one eye) Rapidly progressive glaucoma (as assessed by more than -1.00 MD drop over&#xD;
        three months of visual field testing) Non-native English Speakers&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <reference>
    <citation>Grewal DS, Mahmoud TH. Autologous Neurosensory Retinal Free Flap for Closure of Refractory Myopic Macular Holes. JAMA Ophthalmol. 2016 Feb;134(2):229-30. doi: 10.1001/jamaophthalmol.2015.5237. No abstract available.</citation>
    <PMID>26720054</PMID>
  </reference>
  <reference>
    <citation>Joussen AM, Walter P, Jonescu-Cuypers CP, Koizumi K, Poulaki V, Bartz-Schmidt KU, Krieglstein GK, Kirchhof B. Retinectomy for treatment of intractable glaucoma: long term results. Br J Ophthalmol. 2003 Sep;87(9):1094-102. doi: 10.1136/bjo.87.9.1094.</citation>
    <PMID>12928275</PMID>
  </reference>
  <reference>
    <citation>Parolini B, Grewal DS, Pinackatt SJ, Baldi A, Di Salvatore A, Besozzi G, Finzi A, Cardillo D, Mahmoud TH. COMBINED AUTOLOGOUS TRANSPLANTATION OF NEUROSENSORY RETINA, RETINAL PIGMENT EPITHELIUM, AND CHOROID FREE GRAFTS. Retina. 2018 Sep;38 Suppl 1(Suppl 1):S12-S22. doi: 10.1097/IAE.0000000000001914.</citation>
    <PMID>29210941</PMID>
  </reference>
  <reference>
    <citation>Ramli N, Htoon HM, Ho CL, Aung T, Perera S. Risk factors for hypotony after transscleral diode cyclophotocoagulation. J Glaucoma. 2012 Mar;21(3):169-73. doi: 10.1097/IJG.0b013e318207091a.</citation>
    <PMID>21336153</PMID>
  </reference>
  <reference>
    <citation>Jain K, Dubey S, Pegu J. Comparison of Efficacy and Complications of Cyclophotocoagulation and Second Glaucoma Drainage Device After Initial Glaucoma Drainage Device Failure. J Glaucoma. 2018 Aug;27(8):e140. doi: 10.1097/IJG.0000000000000955. No abstract available.</citation>
    <PMID>29578892</PMID>
  </reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>January 7, 2019</study_first_submitted>
  <study_first_submitted_qc>January 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 9, 2019</study_first_posted>
  <last_update_submitted>July 15, 2020</last_update_submitted>
  <last_update_submitted_qc>July 15, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Ira Schachar</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glaucoma</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03798145
org study id: 49075
nct id: NCT03798145
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Glaucoma is a leading cause of blindness worldwide. It is caused by persistently elevated
      intraocular pressure causing progressive visual field loss. While a number of conventional
      medical and surgical therapies exist, a significant number of patients fail to respond
      resulting in persistently elevated intraocular pressure and eventual blindness. While outflow
      from the eye primarily occurs through the front of the eye, there is an often overlooked
      pathway to remove fluid that is beneath the retina. Surgical removal of retina to create
      paths for outflow (surgical retinotomy) in areas damaged by glaucoma can provide access to
      this alternative outflow pathway thereby reducing intraocular pressure and halting the vision
      loss.
The goal of this study is to demonstrate that focal surgical retinotomies (holes in the
      retina) can result in predictable and lasting reduction in intraocular pressure while
      eliminating the risks associated with surgical retinectomy (broad areas of retinal removal).

      In the late 1990s and early 2000s, Joussen et al pioneered a technique to lower intraocular
      pressure in patients with advanced untreatable glaucoma. All patients had intraocular
      pressures on average above 40 that were unresponsive to any available treatments. Forty-four
      patients underwent broad areas of retinal removal (retinectomy). All patients exhibited
      dramatic reductions in intraocular pressure which were maintained for 5 years (Joussen 2003).
      Unfortunately, the technique carried significant risks. 1) a subset of patients had
      excessively low intraocular pressure reductions. 2) a subset of patients had secondary
      proliferative vitreoretinopathy (a scarring response) that resulting in retinal deatchment.
      Despite its incredible effectiveness, these risks made clinicians hesitant to adopt the
      technique. Additionally, glaucoma specialists are unable to perform the technical procedures
      required creating a chasm between diagnosing physician (glaucoma specialist) and the treating
      physician (retina specialist). Finally, surgical microtools tools at the time were still in
      their infancy.

      The current proposal attempts to make critical modifications to the technique used by Joussen
      et al. (2003). First and foremost, we plan to use surgical retinotomies (holes in the retina)
      in lieu of a broad surgical retinectomy (broad peripheral retinal removal). This is a
      critical difference. Removal of the peripheral retina to the ora serrata carries significant
      risk of postoperative proliferative vitreoretinopathy. This is largely due to residual
      vitreous which cannot be removed from the far peripheral retina. This residual vitreous
      contracts in the postoperative period causing elevation of the retinectomy edges allowing for
      retinal detachment. Surgical retinotomies (holes in the retina), that do not involve the
      vitreous base are commonly used in retina surgery and do not carry anywhere close to the risk
      of retinal detachment that surgical retinectomy carries. As an example, the majority of
      retinal detachments are repaired by draining fluid through an iatrogenic surgical retinotomy
      (a hole created by the surgeon in the retina). These holes are created in the posterior
      retina and yet are virtually always undetectable by the patient. (Of note, a peripheral
      retinotomy is even harder to detect). More recently, there has been an upsurge of free-flap
      autologous retinal transplantation for macular holes (Grewal 2016) and macular degeneration
      (Parolini 2018). In these surgical procedures, an area of peripheral retina is removed and
      transplanted to the macula. The site of removal leaves a hole in the retina. In these studies
      the rate of redetachment in patients in whom a retinotomy was created is no higher than that
      of other standard retina surgeries. It is therefore clear that creation of retinal holes
      (retinotomy) is far different in terms of long-term risks than broad retinal removal to the
      ora serrata (retinectomy). Additionally, this increase in retina transplantation has been
      made possible by the microsurgical surgical tools that are now available. However, in the
      case of both the retinal detachment repair and autologous transplantation, the retinotomy
      size is not sufficient to induce intraocular pressure lowering effects. We therefore seek to
      build upon the original work from Joussen et al (2003) which showed that retina removal can
      have dramatic intraocular pressure lowering effects, but seek to use surgical retinotomies
      (holes in the retina) to achieve this retinal removal thereby avoiding his surgical
      complications while capitalizing on the long-term efficacy. By varying the size and number of
      surgical retinotomy, we will be able to provide a normogram for effective prediction of
      intraocular pressure lowering effects. By effectively predicting the magnitude of this
      surgical procedure, ophthalmologists will have a predictable and reliable method for treating
      glaucoma. Furthermore, because a surgical retinotomy does not close, it is predicted to
      provide a life-long effect.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Intraocular Pressure
time frame: 2 years
description: Percentage Reduction in Intraocular Pressure
measure: Visual Field Progression
time frame: 2 years
description: Visual Field Progression on HVF 24-2 or Goldmann Visual Field
arm group label: Surgical Retinotomy
arm group type: Experimental
description: Surgical retinotomy will be constructed in the area of the scotoma.
intervention type: Procedure
intervention name: Surgical Retinotomy
description: Surgical removal of small areas of retinal to increase outflow through the posterior drainage pathway.
arm group label: Surgical Retinotomy
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
citation: Grewal DS, Mahmoud TH. Autologous Neurosensory Retinal Free Flap for Closure of Refractory Myopic Macular Holes. JAMA Ophthalmol. 2016 Feb;134(2):229-30. doi: 10.1001/jamaophthalmol.2015.5237. No abstract available.
PMID: 26720054
citation: Joussen AM, Walter P, Jonescu-Cuypers CP, Koizumi K, Poulaki V, Bartz-Schmidt KU, Krieglstein GK, Kirchhof B. Retinectomy for treatment of intractable glaucoma: long term results. Br J Ophthalmol. 2003 Sep;87(9):1094-102. doi: 10.1136/bjo.87.9.1094.
PMID: 12928275
citation: Parolini B, Grewal DS, Pinackatt SJ, Baldi A, Di Salvatore A, Besozzi G, Finzi A, Cardillo D, Mahmoud TH. COMBINED AUTOLOGOUS TRANSPLANTATION OF NEUROSENSORY RETINA, RETINAL PIGMENT EPITHELIUM, AND CHOROID FREE GRAFTS. Retina. 2018 Sep;38 Suppl 1(Suppl 1):S12-S22. doi: 10.1097/IAE.0000000000001914.
PMID: 29210941
citation: Ramli N, Htoon HM, Ho CL, Aung T, Perera S. Risk factors for hypotony after transscleral diode cyclophotocoagulation. J Glaucoma. 2012 Mar;21(3):169-73. doi: 10.1097/IJG.0b013e318207091a.
PMID: 21336153
citation: Jain K, Dubey S, Pegu J. Comparison of Efficacy and Complications of Cyclophotocoagulation and Second Glaucoma Drainage Device After Initial Glaucoma Drainage Device Failure. J Glaucoma. 2018 Aug;27(8):e140. doi: 10.1097/IJG.0000000000000955. No abstract available.
PMID: 29578892
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Ira Schachar
investigator title: Principal Investigator
mesh term: Glaucoma
sharing ipd: No