All Posts tagged Study

Methodological Insights for Randomized Clinical Trials of Retinitis Pigmentosa

There are no approved drug treatments for autosomal-dominant retinitis pigmentosa.
 
A study of oral Valproic acid (VPA) does not support the use of VPA in the treatment of autosomal-dominant retinitis pigmentosa.
 
The lessons learned from a trial of Valproic acid are:

  • Rigorous evaluation of drug treatment for retinitis pigmentosa is necessary.
  • FDA-approved drugs for other uses can have major adverse effects.
  • Patients vary greatly in their rates of progression of retinitis pigmentosa with identical gene mutations.

“Methodological Insights for Randomized Clinical Trials of Retinitis Pigmentosa”
Lessons Learned from a Trial of Valproic Acid

JAMA Ophthalmol 136:857-858, August 2018
Brian P. Brooks, MD, PhD; Brett Jeffrey, PhD

Full Paper: Methodological Insights for Randomized Clinical Trials of Retinitis Pigmentosa_08-13-18

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Evaluation of Full-Field Electroretinogram Reductions After Ocriplasmin Treatment

Results of the OASIS Trial ERG Substudy

Purpose

To explore a possible association between full-field electroretinograms with vitreomacular adhesion resolution and best-corrected visual acuity as part of the prospective, randomized, double-masked, sham-controlled Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole (OASIS) trial studying ocriplasmin.

Methods

The ERG substudy enrolled 62 of 220 OASIS subjects (randomized 2:1) and analyzed full-field electroretinograms and their association with both vitreomacular adhesion resolution and best-corrected visual acuity from baseline through Month 24. Electroretinogram reductions were defined as acute full-field electroretinogram reductions in amplitude of $40% from baseline occurring at postinjection Day 7 or Day 28.

Results

In the ocriplasmin group, 16/40 (40%) subjects developed ERG reductions, compared to 1/21 (4.8%) in the sham group; 13/16 (81.3%) and 1/1 (100%) resolved by study end, respectively. A total of 11/16 (68.8%) ocriplasmin-treated subjects with ERG reductions achieved vitreomacular adhesion resolution, compared to those without (9/24, 37.5%). The ocriplasmin-treated subjects with ERG reductions also gained more letters on average (11.3 vs. 9.3 letters) from baseline and had a difference of 6.7 letters in mean bestcorrected visual acuity by study end compared to those without ERG reductions.

Conclusion

Ocriplasmin-treated subjects with ERG reductions had a higher rate of vitreomacular adhesion resolution and showed better visual improvement than their counterparts without ERG reductions or sham subjects by study end.

RETINA 38:364–378, 2018

Full Paper: Evaluation of Full-Field Electroretinogram Reductions After Ocriplasmin Treatment
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Accuracy of Diagnostic Imaging Modalities for Classifying Pediatric Eyes as Papilledema Versus Pseudopapilledema

Purpose

To identify the most accurate diagnostic imaging modality for classifying pediatric eyes as papilledema (PE) or pseudopapilledema (PPE).

Design

Prospective observational study.

Subjects

Nineteen children between the ages of 5 and 18 years were recruited. Five children (10 eyes) with PE, 11 children (19 eyes) with PPE owing to suspected buried optic disc drusen (ODD), and 3 children (6 eyes) with PPE owing to superficial ODD were included.

Methods

All subjects underwent imaging with B-scan ultrasonography, fundus photography, autofluorescence, fluorescein angiography (FA), optical coherence tomography (OCT) of the retinal nerve fiber layer (RNFL), and volumetric OCT scans through the optic nerve head with standard spectral-domain (SD OCT) and enhanced depth imaging (EDI OCT) settings. Images were read by 3 masked neuro-ophthalmologists, and the final image interpretation was based on 2 of 3 reads. Image interpretations were compared with clinical diagnosis to calculate accuracy and misinterpretation rates of each imaging modality.

Main Outcome Measures

Accuracy of each imaging technique for classifying eyes as PE or PPE, and misinterpretation rates of each imaging modality for PE and PPE.

Results

Fluorescein angiography had the highest accuracy (97%, 34 of 35 eyes, 95% confidence interval 92%e100%) for classifying an eye as PE or PPE. FA of eyes with PE showed leakage of the optic nerve, whereas eyes with suspected buried ODD demonstrated no hyperfluorescence, and eyes with superficial ODD showed nodular staining. Other modalities had substantial likelihood (30%e70%) of misinterpretation of PE as PPE.

Conclusions

The best imaging technique for correctly classifying pediatric eyes as PPE or PE is FA. Other imaging modalities, if used in isolation, are more likely to lead to misinterpretation of PE as PPE, which could potentially result in failure to identify a life-threatening disorder causing elevated intracranial pressure and papilledema.

Full Paper: Accuracy of Diagnostic Imaging Modalities for Classifying Pediatric Eyes as Papilledema Versus Pseudopapilledema
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Natural Course of Patients Discontinuing Treatment for Age-Related Macular Degeneration and Factors Associated with Visual Prognosis

Purpose

To evaluate the 24-month natural course of visual changes in patients discontinuing treatment despite persistent or recurrent fluid and factors predictive of visual prognosis.

Methods

This retrospective, observational study included 35 patients (35 eyes) who initially received anti-vascular endothelial growth factor treatment for neovascular age-related macular degeneration (AMD), but discontinued treatment despite persistent or recurrent fluid. The best-corrected visual acuity (BCVA) at treatment discontinuation was determined and compared with the 24-month BCVA, which was then compared between polypoidal choroidal vasculopathy and other neovascular age-related macular degeneration subtypes. Baseline characteristics predictive of visual outcome and the degree of visual change were also analyzed.

Results

The mean number of anti-vascular endothelial growth factor injections before treatment discontinuation was 4.0 ± 1.6. The mean logarithm of minimal angle of resolution of BCVA at treatment discontinuation and that at 24 months were 1.02 ± 0.20 (Snellen equivalents = 20/209) and 1.60 ± 0.56 (20/796), respectively (P , 0.001). The 24-month BCVA was not different between polypoidal choroidal vasculopathy and other neovascular age-related macular degeneration subtypes (P = 0.803). The type of fluid (intraretinal fluid vs. no intraretinal fluid) was predictive of 24-month BCVA (P = 0.004) and the degree of changes in BCVA (P = 0.043).

Conclusion

Marked deterioration in visual acuity was noted in patients discontinuing treatment, regardless of neovascular age-related macular degeneration subtypes. The presence of intraretinal fluid was associated with worse visual prognosis, suggesting that patients with intraretinal fluid should be strongly warned about their poor prognosis before they decide to discontinue treatment.

Full Paper: Natural Course of Patients Discontinuing Treatment for Age-Related Macular Degeneration and Factors Associated with Visual Prognosis
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Comparison of Pneumatic Retinopexy and Scleral Buckle for Primary Rhegmatogenous Retinal Detachment Repair

Background and Objective

To compare pneumatic retinopexy (PR) and scleral buckle for the repair of primary rhegmatogenous retinal detachment.

Patients and Methods

Retrospective analysis of 90 patients undergoing surgery for primary rhegmatogenous retinal detachment, with 46 patients undergoing PR compared with 44 patients undergoing scleral buckle procedure (SBP).

Results

Both groups had similar baseline characteristics. Single surgery reattachment rate was 95.5% with SBP and 67% with PR (P = .00057). Final reattachment rate was 100% with SBP and 97.8% with PR. A final visual acuity (VA) of 20/40 or better occurred in 89% of patients with SBP and 72% of patients with PR (P = .04). PR and SBP had a similar mean VA if the primary procedures were successful, whereas those patients with unsuccessful PR had lower mean final acuities.

Conclusions

This study demonstrates that SBP has a significantly higher rate of single surgery reattachment than PR, along with improved final VA. Initial success of PR may be an important predictor of final visual outcome.

Full Paper: Comparison of Pneumatic Retinopexy and Scleral Buckle for Primary Rhegmatogenous Retinal Detachment Repair
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Macular Degeneration and Aspirin Use

Recent press releases regarding the potential adverse effects of aspirin on macular degeneration have caused patients with age-related macular degeneration (AMD) to discontinue their aspirin use without consulting their physician.1,2 There are many benefits to aspirin use, and therefore many reasons patients should continue taking the recommended aspirin dose prescribed by their primary physician or cardiologists. As with any treatment, it is important to weigh the risk/benefit ratio of aspirin use, especially in generally elderly and high-risk populations. The benefits of aspirin have long been well documented and highly recommended for the prevention and treatment of cardiovascular diseases (CVDs), such as myocardial infarction, stroke, and death. The recent retrospective epidemiological eye studies suggesting that aspirin use may exacerbate macular degeneration are based on three limited studies, while the benefits of aspirin use for macular degeneration patients have been suggested in larger studies, including Age-Related Eye Disease Study (AREDS), the Physicians Health Study (PHS), Women’s Health Study (WHS).1–4 Therefore, the data regarding the effects of aspirin on AMD are conflicting and inconclusive.

Full Paper: Macular Degeneration and Aspirin Use
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YAG Laser Vitreolysis vs Sham YAG Vitreolysis for Symptomatic Vitreous Floaters

Floaters become more prevalent with age because of degenerative vitreous changes that occur throughout life. In youth, hyaluronan keeps collagen fibrils separated in the vitreous cavity and thus maintains transparency of the vitreous. However, with time, hyaluronan dissociates from collagen, causing cross-linking and aggregation of collagen with fibrous structures that scatter light—a process known as vitreous liquefaction.1-3

Clinically, a posterior vitreous detachment (PVD) is often marked by a degree of fibroglial tissue known as a Weiss ring that is free floating over the optic nerve. A PVD allows the vitreous body to move when the head or eye moves, and thus, the Weiss ring and vitreous opacities cast shadows onto the retina that are perceived as floaters.

A PVD is present in approximately 65% of patients reaching the age of 65 years.4,5 Although most patients grow accustomed to the visual disturbance associated with Weiss rings and other floaters, many find them bothersome.6 Floaters can reduce contrast sensitivity and quality of life.7,8

Three management options exist for symptomatic floaters: patient education and observation, pars plana vitrectomywith a 1-incision Intrector (in which a 1-incision, limited core vitrectomy is performed while visualizing through an indirect ophthalmoscope; Insight Instruments) or a standard 3-port vitrector, and YAG vitreolysis.

Existing literature assessing the effect of YAG laser on the properties of rabbit vitreous has suggested that pathologic disruption may occur with laser application in the middle or posterior vitreous.9 There are limited published studies on the effect of YAG vitreolysis for treating symptomatic floaters in humans. Small, uncontrolled cases series6,10,11 assessing YAG vitreolyisis report some symptomatic success and suggest a good safety profile. No prospective, sham-controlled trials have been performed, to our knowledge. This is particularly important because of the subjective nature of floater related visual disturbance and the potential of placebo effect confounding the efficacy of treatment. Research by Karickhoff12 showed the most robust outcomes when treating Weiss rings. Therefore, the current study evaluated YAG vitreolysis in patients with symptomatic Weiss rings.

Full Paper: YAG Laser Vitreolysis vs Sham YAG Vitreolysis for Symptomatic Vitreous Floaters
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Stem Cell Clinics

Recent practices at “stem cell clinics” in the United States have resulted in blinding complications for three patients who underwent bilateral intravitreal injection of adipose-derived stem cell injections for dry age-related macular degeneration, as recently published in the New England Journal of Medicine: patient’s vision went from 20/30 to no light perception and 20/200.

The “stem cell clinics” problem is that they provide unproven, unregulated, and costly ($50,000) treatment for a variety of disorders and raise high concern for patients.

By having studies listed on clinicaltrials.gov, “stem cell clinics” seemingly bolster their legitimacy to patients. clinicaltrials.gov website is simply a repository of clinical studies and does not judge the merits of the listed studies.

It is important to encourage patients to speak with a “trusted healthcare professional” prior to enrolling in a study. Exploring the difference between the positive stem cell research and the activities carried out at “stem cell clinics” is essential in preventing such catastrophic outcomes.

Further regulation of these “stem cell clinics” is also necessary to help prevent similar outcomes in the future.

References

“Implications of Stem Cell Clinics for Retina Patients and Clinical Trials” Retinal Physician, Volume 14, Issue: May 2017, page(s) 32,40: Ajay E. Kuriyan, MD, MS; Thomas Albini, MD; Harry W. Flynn, Jr., MD

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“The Growing ‘Stem Cell Clinic’ Problem” American Journal of Ophthalmology, Volume 177, xix–xx: Ajay E. Kuriyan, MD, MS; Thomas Albini, MD; Harry W. Flynn, Jr., MD

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Retinal Physician Clinical Trial Update

Dry AMD

Study: A Phase 2/3 Trial to Assess the Safety and Efficacy of Intravitreous Administration of Zimura (Anti-C5 Aptamer) in Subjects With Geographic Atrophy Secondary to Dry Age-Related Macular Degeneration

Sponsor: Ophthotech

Purpose: To evaluate the safety and efficacy of intravitreous administration of Zimura when administered in subjects with geographic atrophy (GA) secondary to dry age-related macular degeneration

Design: Randomized, Safety/Efficacy, Parallel Assignment, Double Blind

Number of Patients: 300

Inclusion Criteria: Diagnosis of non-foveal GA secondary to dry AMD

Exclusion Criteria: Retinal atrophy involving the fovea; evidence of CNV; any prior treatment for AMD or any prior intravitreal treatment for any indication in either eye, except oral supplements of vitamins and minerals; any intraocular surgery or thermal laser within 3 months of trial entry; any prior thermal laser in the macular region, regardless of indication; any ocular or periocular infection in the 12 weeks prior to entry; previous therapeutic radiation in the region of the study eye; any sign of diabetic retinopathy in either eye

Full Paper: Retinal Physician Clinical Trial Update
(206K PDF)

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Trends of Anti-Vascular Endothelial Growth Factor Use in Ophthalmology Among Privately Insured and Medicare Advantage Patients

Purpose: To characterize the first 10 years of intravitreal anti-vascular endothelial growth factor (VEGF) medication use for ophthalmic disease, including bevacizumab, ranibizumab, and aflibercept.

Design: A retrospective cohort study using administrative claims data from January 1, 2006 to December 31, 2015.

Subjects: Total of 124 835 patients 18 years of age or over in the United States.

Methods: OptumLabs Data Warehouse, which includes administrative claims data for over 100 million commercially insured and Medicare Advantage individuals, was used to identify patients receiving intravitreal anti-VEGF injections based on Current Procedural Terminology codes.

Main Outcome Measures: Total and annual numbers of intravitreal anti-VEGF injections, as well as injections per 1000 enrolled patients per general category of ophthalmic disease, overall and for each available medication.

Results: There were 959 945 anti-VEGF injections among 124 835 patients from 2006 to 2015. Among all injections, 64.6% were of bevacizumab, 22.0% ranibizumab, and 13.4% aflibercept; 62.7% were performed to treat age-related macular degeneration (AMD), 16.1% to treat diabetic retinal diseases (including 0.9% of all injections that were for proliferative diabetic retinopathy), 8.3% to treat retinal vein occlusions, and 12.9% for all other uses. Use of bevacizumab and ranibizumab for AMD plateaued as of 2011/2012 and decreased thereafter (in 2006, 58.8 and 35.3 injections/1000 AMD patients, respectively; in 2015, 294.4 and 100.7 injections/1000), whereas use of aflibercept increased (1.1 injections/1000 AMD patients in 2011 to 183.0 injections/1000 in 2015). Bevacizumab use increased each year for diabetic retinal disease (2.4 injections/1000 patients with diabetic retinal disease in 2009 to 13.6 per 1000 in 2015) while that of ranibizumab initially increased significantly and then declined after 2014 (0.1 in 2009 to 4.0 in 2015). Aflibercept use increased each year in patients with diabetic etinal diseases and retinal vein occlusions (both >0.1 per 1000 retinal vein occlusion patients in 2011, 5.6 and 140.2 in 2015).

Conclusions: Intravitreal injections of anti-VEGF medications increased annually from 2006 to 2015. Bevacizumab was the most common medication used, despite its lacking U.S. Food and Drug Administration approval to treat ophthalmic disease, and AMD was the most common condition treated. Ranibizumab use declined after 2014 while both the absolute and relative use of bevacizumab and aflibercept increased. Ophthalmology 2017;124:352-358 ª 2016 by the American Academy of Ophthalmology

Full Paper: Trends of Anti-Vascular Endothelial Growth Factor Use in Ophthalmology Among Privately Insured and Medicare Advantage Patients
(599K PDF)

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