Treatment for presumed ocular histoplasmosis (HANDLE)

Institution: Retina Associates of Kentucky

Author/principal investigator: John W. Kitchens, MD

Abstract/statement of the trial’s goals

This study is designed to monitor safety outcomes for patients being treated with intravitreal aflibercept injections for choroidal neovascularization secondary to presumed ocular histoplasmosis syndrome.

ClinicalTrials.gov identifier: NCT01790893

Study population: 40

Inclusion criteria

  • Age older than 18 years.
  • Active choroidal neovascularization (CNV) secondary to presumed ocular histoplasmosis demonstrated by active leakage on fluorescein angiography with spectral domain OCT evidence of subretinal or intraretinal fluid or PED.
  • Active CNV may also be defined as demonstrating active subretinal hemorrhage.
  • ETDRS best corrected visual acuity 20/20 to 20/320.

Exclusion criteria

  • Age younger than 18 years.
  • CNV due to causes other than presumed ocular histoplasmosis.
  • Previous treatment in the study eye within 6 months prior to day 1.
  • Acute cardiovascular event requiring hospitalization within the past 3 months.
  • More than five intravitreal injections of anti-VEGF therapy within previous 12 months.
  • Clinical evidence of any ocular condition other than ocular histoplasmosis.
  • History of allergy to fluorescein.
  • Pregnant (or planning on becoming pregnant within the next 13 months) or breastfeeding women.
  • Sexually active men or women who are not willing to practice more than one form of contraception during the next 13 months.
  • Anticipated or previous (within previous 3 months) systemic anti-VEGF therapy.

Enrollment status: Currently recruiting participants.

A note from the institution regarding the value of this trial

The benefit of anti-VEGF therapy for choroidal neovascularization secondary to ocular histoplasmosis syndrome (OHS) has been demonstrated previously. The benefit of this trial is that two different dosing strategies are utilized. The standard VIEW 1/2 dosing paradigm: three monthly injections followed by every 2 months will be compared to an as-needed treatment strategy. This will help to identify the best approach to this clinical entity.

Eye Injections of bevacizumab to see if medication helps to lower risk of scar tissue development in the retina and repeated retinal detachment

Institution: Wills Eye

Author/principal investigator: Jason Hsu, MD

Abstract/statement of the trial’s goals

The objective of this pilot study is to determine the effect of intraoperative and serial postoperative intravitreal bevacizumab injections on prevention of retinal redetachment and recurrence of proliferative vitreoretinopathy (PVR) in a cohort of patients presenting with retinal detachment due to PVR.

ClinicalTrials.gov identifier: NCT01860586

Study population: 20

Inclusion criteria

  • Age older than 18 years.
  • Ability to provide written informed consent and comply with study assessments for the full duration of the study.
  • Undergoing pars plana vitrectomy with or without scleral buckling for recurrent RD due to PVR with planned silicone oil instillation.

Exclusion criteria

  • Prior anti-VEGF injections within 3 months of retinal detachment surgery.
  • Traction retinal detachment due to proliferative diabetic retinopathy.
  • Inability to flatten retina completely intraoperatively.
  • Known allergy or contraindication to intravitreal bevacizumab.

Enrollment status: Currently recruiting participants.

A note from the institution regarding the value of this trial

Proliferative vitreoretinopathy (PVR) is one of the major causes of recurrent retinal detachment (RD) following initially successful surgical repair. Currently, no medical interventions have been found that conclusively lower the risk of PVR development.

Several studies have suggested a potential role for vascular endothelial growth factor (VEGF) in the pathogenesis of PVR. Vitreous levels of VEGF have been reported to be significantly higher in cases of RD with PVR compared to eyes with uncomplicated RD. Immunohistochemical studies of epiretinal membranes from PVR cases have also demonstrated the presence of VEGF and its receptors in the majority of these samples. While VEGF has been clearly implicated as a potent angiogenic stimulator associated with neovascularization and vascular leakage, one study has discovered an alternatively spliced antiangiogenic isoform of VEGF. This form is generally more prevalent in subretinal fluid of patients with PVR, which may explain the lack of neovascularization in PVR membranes. More recently, anti-VEGF therapy has been reported to reduce the bioactivity of vitreous from patients and experimental animals with PVR as well as protect from PVR development in a rabbit model. Interestingly, the mechanism of action appears to involve inhibition of platelet-derived growth factor receptor α. The activation of this receptor is required for development of experimental PVR and has been associated with this disease in humans.

Based on these findings, it is possible that blocking VEGF in patients with RD from PVR may help lower the risk of recurrent RD following surgical intervention through the prevention of reproliferation of avascular membranes.

Institution: Retina Associates of Kentucky

Author/principal investigator: John W. Kitchens, MD

Abstract/statement of the trial’s goals

This study is designed to monitor safety outcomes for patients being treated with intravitreal aflibercept injections for choroidal neovascularization secondary to presumed ocular histoplasmosis syndrome.

ClinicalTrials.gov identifier: NCT01790893

Study population: 40

Inclusion criteria

  • Age older than 18 years.
  • Active choroidal neovascularization (CNV) secondary to presumed ocular histoplasmosis demonstrated by active leakage on fluorescein angiography with spectral domain OCT evidence of subretinal or intraretinal fluid or PED.
  • Active CNV may also be defined as demonstrating active subretinal hemorrhage.
  • ETDRS best corrected visual acuity 20/20 to 20/320.

Exclusion criteria

  • Age younger than 18 years.
  • CNV due to causes other than presumed ocular histoplasmosis.
  • Previous treatment in the study eye within 6 months prior to day 1.
  • Acute cardiovascular event requiring hospitalization within the past 3 months.
  • More than five intravitreal injections of anti-VEGF therapy within previous 12 months.
  • Clinical evidence of any ocular condition other than ocular histoplasmosis.
  • History of allergy to fluorescein.
  • Pregnant (or planning on becoming pregnant within the next 13 months) or breastfeeding women.
  • Sexually active men or women who are not willing to practice more than one form of contraception during the next 13 months.
  • Anticipated or previous (within previous 3 months) systemic anti-VEGF therapy.

Enrollment status: Currently recruiting participants.

A note from the institution regarding the value of this trial

The benefit of anti-VEGF therapy for choroidal neovascularization secondary to ocular histoplasmosis syndrome (OHS) has been demonstrated previously. The benefit of this trial is that two different dosing strategies are utilized. The standard VIEW 1/2 dosing paradigm: three monthly injections followed by every 2 months will be compared to an as-needed treatment strategy. This will help to identify the best approach to this clinical entity.

Eye Injections of bevacizumab to see if medication helps to lower risk of scar tissue development in the retina and repeated retinal detachment

Institution: Wills Eye

Author/principal investigator: Jason Hsu, MD

Abstract/statement of the trial’s goals

The objective of this pilot study is to determine the effect of intraoperative and serial postoperative intravitreal bevacizumab injections on prevention of retinal redetachment and recurrence of proliferative vitreoretinopathy (PVR) in a cohort of patients presenting with retinal detachment due to PVR.

ClinicalTrials.gov identifier: NCT01860586

Study population: 20

Inclusion criteria

  • Age older than 18 years.
  • Ability to provide written informed consent and comply with study assessments for the full duration of the study.
  • Undergoing pars plana vitrectomy with or without scleral buckling for recurrent RD due to PVR with planned silicone oil instillation.

Exclusion criteria

  • Prior anti-VEGF injections within 3 months of retinal detachment surgery.
  • Traction retinal detachment due to proliferative diabetic retinopathy.
  • Inability to flatten retina completely intraoperatively.
  • Known allergy or contraindication to intravitreal bevacizumab.

Enrollment status: Currently recruiting participants.

A note from the institution regarding the value of this trial

Proliferative vitreoretinopathy (PVR) is one of the major causes of recurrent retinal detachment (RD) following initially successful surgical repair. Currently, no medical interventions have been found that conclusively lower the risk of PVR development.

Several studies have suggested a potential role for vascular endothelial growth factor (VEGF) in the pathogenesis of PVR. Vitreous levels of VEGF have been reported to be significantly higher in cases of RD with PVR compared to eyes with uncomplicated RD. Immunohistochemical studies of epiretinal membranes from PVR cases have also demonstrated the presence of VEGF and its receptors in the majority of these samples. While VEGF has been clearly implicated as a potent angiogenic stimulator associated with neovascularization and vascular leakage, one study has discovered an alternatively spliced antiangiogenic isoform of VEGF. This form is generally more prevalent in subretinal fluid of patients with PVR, which may explain the lack of neovascularization in PVR membranes. More recently, anti-VEGF therapy has been reported to reduce the bioactivity of vitreous from patients and experimental animals with PVR as well as protect from PVR development in a rabbit model. Interestingly, the mechanism of action appears to involve inhibition of platelet-derived growth factor receptor α. The activation of this receptor is required for development of experimental PVR and has been associated with this disease in humans.

Based on these findings, it is possible that blocking VEGF in patients with RD from PVR may help lower the risk of recurrent RD following surgical intervention through the prevention of reproliferation of avascular membranes.