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The Cochrane Database of Systematic... Oct 2017Symptomatic vitreomacular adhesion (sVMA) is a recognised cause of visual loss and by tradition has been managed by pars plana vitrectomy (PPV). A less invasive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Symptomatic vitreomacular adhesion (sVMA) is a recognised cause of visual loss and by tradition has been managed by pars plana vitrectomy (PPV). A less invasive alternative to surgery in some people is enzymatic vitreolysis, using an intravitreal injection of ocriplasmin.
OBJECTIVES
To assess the efficacy and safety of ocriplasmin compared to no treatment, sham or placebo for the treatment of sVMA.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 1), MEDLINE Ovid (1946 to 24 February 2017), Embase Ovid (1947 to 24 February 2017), PubMed (1946 to 24 February 2017), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 24 February 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 24 February 2017 and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 24 February 2017. We did not use any date or language restrictions in the electronic searches for trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of people with sVMA. The intervention was intravitreal ocriplasmin 125 μg injection, and this was compared to placebo or sham injection (control). Placebo was defined as a single intravitreal injection of 0.10 mL placebo with identical drug vehicle diluted with saline. A sham injection was defined as the syringe hub or blunt needle touching the conjunctiva to simulate an injection.
DATA COLLECTION AND ANALYSIS
Two authors independently selected relevant trials, assessed methodological quality and extracted data. We graded the certainty of the evidence using the GRADE approach.
MAIN RESULTS
This review included four RCTs conducted in Europe and the USA with a total of 932 eyes of 932 participants. Participants were 18 to 97 years of age, with evidence of focal vitreomacular adhesion (VMA) on optical coherence tomography (OCT) imaging, with a best corrected visual acuity (BCVA) of 20/25 or worse in the study eye and 20/400 or better in the fellow eye. The interventions compared were intravitreal ocriplasmin versus sham (two RCTs) or placebo (two RCTs) injection. Both sham and placebo injection were classified as the control group. The main outcome measures were assessed at 28 days and six months. Overall, we judged the studies to have a low or unclear risk of bias. All four RCTs were sponsored by the manufacturers of ocriplasmin.Compared with control, ocriplasmin treatment was more likely to result in VMA release within 28 days (risk ratio (RR) 3.46, 95% confidence interval (CI) 2.00 to 6.00; 859 eyes, 4 RCTs, high-certainty evidence). Approximately 97/1000 eyes will have VMA release within 28 days without treatment. An additional 237 eyes will have VMA release within 28 days for every 1000 eyes treated with ocriplasmin (95% CI 96 more to 482 more).Treatment with ocriplasmin was also more likely to result in macular hole closure (RR 2.87, 95% CI 1.50 to 5.51; 229 eyes, 3 RCTs, high-certainty evidence). Approximately 123/1000 eyes with macular holes will have closure with no treatment. An additional 231 eyes will have macular hole closure for every 1000 eyes treated with ocriplasmin (95% CI 62 more to 556 more).Eyes receiving ocriplasmin were also more likely to have complete posterior vitreous detachment (PVD) within 28 days (RR 2.94, 95% CI 1.39 to 6.24; 689 eyes, 3 RCTs, high-certainty evidence). Approximately 40/1000 eyes will have complete PVD within 28 days without treatment. An additional 78 eyes will have complete PVD within 28 days for every 1000 eyes treated with ocriplasmin (95% CI 16 more to 210 more).Eyes receiving ocriplasmin were more likely to achieve 3-line or greater improvement in BCVA at six months (RR 1.95, 95% CI 1.07 to 3.53; 674 eyes, 3 RCTs, moderate-certainty evidence). Approximately 61/1000 eyes will have a 3-line or greater improvement in BCVA at six months without treatment. An additional 58 eyes will have 3-line or greater improvement in BCVA at six months for every 1000 eyes treated with ocriplasmin (95% CI 9 more to 154 more).Receiving ocriplasmin also reduced the requirement for vitrectomy at six months (RR 0.67, 95% CI 0.50 to 0.91; 689 eyes, 3 RCTs, moderate-certainty evidence). Approximately 265/1000 eyes will require vitrectomy at six months without treatment and 87 fewer eyes will require vitrectomy for every 1000 eyes treated with ocriplasmin (95% CI 24 fewer to 132 fewer).Treatment with ocriplasmin resulted in a greater improvement in validated Visual Function Questionnaire form score at six months (mean improvement difference 2.7 points, 95% CI 0.8 to 4.6; 652 eyes, 2 RCTs, moderate-certainty evidence).Eyes receiving ocriplasmin were more likely to have an adverse event (RR 1.22, 95% CI 1.09 to 1.37, 909 eyes, 4 RCTs, moderate-certainty evidence). Approximately 571/1000 eyes will have an adverse event with sham or placebo injection and 106 more eyes will have an adverse event for every 1000 eyes treated with ocriplasmin (95% CI 52 more to 212 more).
AUTHORS' CONCLUSIONS
Evidence from a limited number of RCTs suggests that ocriplasmin is useful in the treatment of sVMA. However, up to 20% of eyes treated with ocriplasmin will still require additional treatment with PPV within six months. There were more ocular adverse events in eyes treated with ocriplasmin than control (sham or placebo injection) treatment. Many of these adverse events, particularly vitreous floaters and photopsia, are known to be associated with posterior vitreous detachment. At present however, there is minimal published long-term safety data on eyes treated with ocriplasmin. Further large RCTs comparing ocriplasmin with other management options for sVMA would be beneficial.
Topics: Adult; Aged; Aged, 80 and over; Fibrinolysin; Fibrinolytic Agents; Humans; Intravitreal Injections; Middle Aged; Peptide Fragments; Randomized Controlled Trials as Topic; Retinal Diseases; Time Factors; Tissue Adhesions; Visual Acuity; Vitrectomy; Vitreous Body; Vitreous Detachment
PubMed: 29040800
DOI: 10.1002/14651858.CD011874.pub2 -
Ophthalmology and Therapy Dec 2017The purpose of this report is to describe a case of macular hole development after vitrectomy for floaters with induction of posterior vitreous detachment.
INTRODUCTION
The purpose of this report is to describe a case of macular hole development after vitrectomy for floaters with induction of posterior vitreous detachment.
CASE REPORT
A 44-year-old otherwise healthy man presented with visually debilitating floaters in his right eye; these had been present for more than 2 years. Preoperative examination was unremarkable in both eyes, apart from some degree of vitreous degeneration in the right eye. Preoperative visual acuity was 20/20 bilaterally. A 25-gauge transconjunctival sutureless pars plana complete vitrectomy with induction of posterior vitreous detachment was performed in the right eye. Upon examination 1 month after surgery, a small full-thickness macular hole was detected in the right eye. Visual acuity was diminished to 20/80. The macular hole was closed after a second vitrectomy with internal limiting membrane peeling and gas tamponade.
CONCLUSION
Macular hole development should be listed as a possible complication of vitrectomy for visually debilitating floaters when a posterior vitreous detachment is induced during surgery.
PubMed: 29022285
DOI: 10.1007/s40123-017-0111-9 -
JAMA Ophthalmology Sep 2017Vitreous floaters are common and can worsen visual quality. YAG vitreolysis is an untested treatment for floaters. (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
Vitreous floaters are common and can worsen visual quality. YAG vitreolysis is an untested treatment for floaters.
OBJECTIVE
To evaluate YAG laser vitreolysis vs sham vitreolysis for symptomatic Weiss ring floaters from posterior vitreous detachment.
DESIGN, SETTING, AND PARTICIPANTS
This single-center, masked, sham-controlled randomized clinical trial was performed from March 25, 2015, to August 3, 2016, in 52 eyes of 52 patients (36 cases and 16 controls) treated at a private ophthalmology practice.
INTERVENTIONS
Patients were randomly assigned to YAG laser vitreolysis or sham YAG (control).
MAIN OUTCOMES AND MEASURES
Primary 6-month outcomes were subjective change measured from 0% to 100% using a 10-point visual disturbance score, a 5-level qualitative scale, and National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25). Secondary outcomes included objective change assessed by masked grading of color fundus photography and Early Treatment Diabetic Retinopathy Study best-corrected visual acuity.
RESULTS
Fifty-two patients (52 eyes; 17 men and 35 women; 51 white and 1 Asian) with symptomatic Weiss rings were enrolled in the study (mean [SD] age, 61.4 [8.0] years for the YAG laser group and 61.1 [6.6] years for the sham group). The YAG laser group reported greater symptomatic improvement (54%) than controls (9%) (difference, 45%; 95% CI, 25%-64%; P < .001). In the YAG laser group, the 10-point visual disturbance score improved by 3.2 vs 0.1 in the sham group (difference, -3.0; 95% CI, -4.3 to -1.7; P < .001). A total of 19 patients (53%) in the YAG laser group reported significantly or completely improved symptoms vs 0 individuals in the sham group (difference, 53%; 95% CI, 36%-69%, P < .001). Compared with sham, NEI VFQ-25 revealed improved general vision (difference, 16.3; 95% CI, 0.9-31.7; P = .04), peripheral vision (difference, 11.6; 95% CI, 0.8-22.4; P = .04), role difficulties (difference, 17.3; 95% CI, 8.0-26.6; P < .001), and dependency (difference, 5.6; 95% CI, 0.5-10.8; P = .03) among the YAG laser group. Best-corrected visual acuity changed by -0.2 letters in the YAG laser group and by -0.6 letters in sham group (difference, 0.4; 95% CI, -6.5 to 5.3; P = .94). No differences in adverse events between groups were identified.
CONCLUSIONS AND RELEVANCE
YAG laser vitreolysis subjectively improved Weiss ring-related symptoms and objectively improved Weiss ring appearance. Greater confidence in these outcomes may result from larger confirmatory studies of longer duration.
TRIAL REGISTRATION
clinicaltrials.gov NCT02897583.
Topics: Adult; Aged; Double-Blind Method; Eye Diseases; Female; Humans; Laser Therapy; Lasers, Solid-State; Male; Middle Aged; Sickness Impact Profile; Surveys and Questionnaires; Visual Acuity; Vitrectomy; Vitreous Body; Vitreous Detachment
PubMed: 28727887
DOI: 10.1001/jamaophthalmol.2017.2388 -
Cancer Medicine Aug 2017To establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety profile, and anti-tumor efficacy of RAF265. We conducted a multicenter, open-label,...
A first-in-human phase I, multicenter, open-label, dose-escalation study of the oral RAF/VEGFR-2 inhibitor (RAF265) in locally advanced or metastatic melanoma independent from BRAF mutation status.
To establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety profile, and anti-tumor efficacy of RAF265. We conducted a multicenter, open-label, phase-I, dose-escalation trial of RAF265, an orally available RAF kinase/VEGFR-2 inhibitor, in patients with advanced or metastatic melanoma. Pharmacokinetic (PK) analysis, pharmacodynamics (PD) and tumor response assessment were conducted. We evaluated metabolic tumor response by 18[F]-fluorodeoxyglucose-positron-emission tomography (FDG-PET), tissue biomarkers using immunohistochemistry (IHC), and modulators of angiogenesis. RAF265 has a serum half-life of approximately 200 h. The MTD was 48 mg once daily given continuously. Among 77 patients, most common treatment-related adverse effects were fatigue (52%), diarrhea (34%), weight loss (31%) and vitreous floaters (27%). Eight of 66 evaluable patients (12.1%) had an objective response, including seven partial and one complete response. Responses occurred in BRAF-mutant and BRAF wild-type (WT) patients. Twelve of 58 (20.7%) evaluable patients had a partial metabolic response. On-treatment versus pretreatment IHC staining in 23 patients showed dose-dependent p-ERK inhibition. We observed a significant temporal increase in placental growth factor levels and decrease in soluble vascular endothelial growth factor receptor 2 (sVEGFR-2) levels in all dose levels. RAF265 is an oral RAF/VEGFR-2 inhibitor that produced antitumor responses, metabolic responses, and modulated angiogenic growth factor levels. Antitumor activity occurred in patients with BRAF-mutant and BRAF-WT disease. Despite low activity at tolerable doses, this study provides a framework for the development of pan-RAF inhibitors and modulators of angiogenesis for the treatment of melanoma.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers; Drug Monitoring; Female; Humans; Imidazoles; Male; Maximum Tolerated Dose; Melanoma; Middle Aged; Molecular Targeted Therapy; Mutation; Neoplasm Metastasis; Neoplasm Staging; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Pyridines; Treatment Outcome
PubMed: 28719152
DOI: 10.1002/cam4.1140 -
Case Reports in Ophthalmology 2017We report a case of rapid cataract progression after Nd:YAG vitreolysis for vitreous floaters.
PURPOSE
We report a case of rapid cataract progression after Nd:YAG vitreolysis for vitreous floaters.
CASE REPORT
A 55-year-old man presented with acute onset of blurred vision following Nd:YAG vitreolysis for symptomatic floaters in the left eye. His initial best corrected visual acuity (BCVA) was 20/1,000 in the left eye. Ocular examinations showed frost-like opacities of the lens and a suspected break of the posterior capsule in the left eye. There were no detectable retinal lesions. Cataract surgery was then arranged. Posterior capsular rupture and vitreous loss occurred during surgery, which required a subsequent pars plana vitrectomy. After the surgery, BCVA in the left eye gradually improved to 20/20 and was maintained during a 1-year follow-up period.
CONCLUSION
Crystalline lens injuries and rapid cataract progression may occur following Nd:YAG vitreolysis. While dealing with this type of complicated cataract, clinicians should be aware of the possibility of posterior lens capsule rupture during surgery and the need for combined vitrectomy.
PubMed: 28626418
DOI: 10.1159/000477159 -
The Cochrane Database of Systematic... Jun 2017The vitreous is the clear jelly of the eye and contains fine strands of proteins. Throughout life the composition of this vitreous changes, which causes the protein... (Review)
Review
BACKGROUND
The vitreous is the clear jelly of the eye and contains fine strands of proteins. Throughout life the composition of this vitreous changes, which causes the protein strands in it to bundle together and scatter light before it reaches the retina. Individuals perceive the shadows cast by these protein bundles as 'floaters'. Some people are so bothered by floaters that treatment is required to control their symptoms. Two major interventions for floaters include Nd:YAG laser vitreolysis and vitrectomy. Nd:YAG laser vitreolysis involves using laser energy to fragment the vitreous opacities via a non-invasive approach. Vitrectomy involves the surgical replacement of the patient's vitreous (including the symptomatic vitreous floaters) with an inert and translucent balanced salt solution, through small openings in the pars plana.
OBJECTIVES
To compare the effectiveness and safety of Nd:YAG laser vitreolysis to pars plana vitrectomy for symptomatic vitreous floaters.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 12), MEDLINE Ovid (1946 to 17 January 2017), Embase Ovid (1947 to 17 January 2017), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 17 January 2017), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 17 January 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 17 January 2017 and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 17 January 2017. We did not use any date or language restrictions in the electronic searches for trials. We also searched conference proceedings to identify additional studies.
SELECTION CRITERIA
We included only randomised controlled trials (RCTs) that compared Nd:YAG laser vitreolysis to pars plana vitrectomy for treatment of symptomatic floaters.
DATA COLLECTION AND ANALYSIS
We planned to use methods recommended by Cochrane. The primary outcome we planned to measure was change in vision-related quality of life from baseline to 12 months, as determined by a vision-related quality of life questionnaire. The secondary outcomes we planned to measure were best corrected logMAR or Snellen visual acuity at 12 months for the treated eye(s) and costs. Adverse outcomes we planned to record were the occurrence of sight-threatening complications by 12 months (asymptomatic retinal tears, symptomatic retinal tears, retinal detachment, cataract formation, and endophthalmitis).
MAIN RESULTS
No studies met the inclusion criteria of this review.
AUTHORS' CONCLUSIONS
There are currently no RCTs that compare Nd:YAG laser vitreolysis with pars plana vitrectomy for the treatment of symptomatic floaters. Properly designed RCTs are needed to evaluate the treatment outcomes from the interventions described. We recommend future studies randomise participants to either a Nd:YAG laser vitreolysis group or a vitrectomy group, with participants in each group assigned to either receive treatment or a sham intervention. Future studies should follow participants at six months and 12 months after the intervention. Also they should use best corrected visual acuity (BCVA) using an Early Treatment of Diabetic Retinopathy Study (ETDRS) chart read at 4 metres, vision-related quality of life (VRQOL), and adverse outcomes as the outcome measures of the trial.
Topics: Eye Diseases; Humans; Lasers, Solid-State; Vitrectomy
PubMed: 28570745
DOI: 10.1002/14651858.CD011676.pub2 -
Case Reports in Ophthalmology 2017Traditionally acceptable methods of anesthesia for vitrectomy surgery are quite varied. However, each of these methods has its own potential for complications that can...
PURPOSE
Traditionally acceptable methods of anesthesia for vitrectomy surgery are quite varied. However, each of these methods has its own potential for complications that can range from minor to severe. The surgery procedure of vitrectomy for symptomatic vitreous floaters is much simpler, mainly reflecting in the nonuse of sclera indentation, photocoagulation, and the apparently short surgery duration. The use of 27-gauge cannulae makes the puncture of the sclera minimally invasive. Hence, retrobulbar anesthesia, due to its rare but severe complications, seemed excessive for this kind of surgery.
METHOD
Three cases of 27-gauge, sutureless pars plana vitrectomy for symptomatic vitreous floaters with topical anesthesia are reported.
RESULTS
The vitrectomy surgeries were successfully performed with topical anesthesia (proparacaine, 0.5%) without operative or postoperative complications. Furthermore, none of the patients experienced apparent pain during or after the surgery.
CONCLUSION
Topical anesthesia can be considered for 27-guage vitrectomy in patients with symptomatic vitreous floaters.
PubMed: 28203195
DOI: 10.1159/000453332 -
Case Reports in Ophthalmology 2016To report a case of endophthalmitis following 27-gauge pars plana vitrectomy for symptomatic vitreous floaters.
PURPOSE
To report a case of endophthalmitis following 27-gauge pars plana vitrectomy for symptomatic vitreous floaters.
METHODS
The clinical course and imaging findings, including fundus optomap, and spectral domain optical coherence tomography of a 24-year-old male patient were documented.
RESULTS
The patient, with a preoperative best-corrected visual acuity (BCVA) of 1.0, developed endophthalmitis following 27-gauge pars plana vitrectomy for symptomatic vitreous floaters. After a series of treatments, including emergent vitreous tap and silicone oil injection, antibiotic treatment, and silicone oil removal, the patient regained a BCVA of 0.6.
CONCLUSION
Although rare, the potential risk of endophthalmitis should be explicitly discussed with patients considering surgical intervention for vitreous floaters.
PubMed: 28101041
DOI: 10.1159/000452733 -
Investigative Ophthalmology & Visual... Jun 2016The goals of this study were to evaluate the safety of office-based vitreous sampling, and determine the utility of these samples with multiplex cytokine analysis.
PURPOSE
The goals of this study were to evaluate the safety of office-based vitreous sampling, and determine the utility of these samples with multiplex cytokine analysis.
METHODS
Vitreous samples were collected from office-based needle aspiration and the rate of adverse events during follow-up was reviewed. The vitreous cytokine concentrations in a subset of patients with diabetic macular edema (DME) were analyzed using a 42 plex-cytokine bead array. These results were compared with vitreous cytokine concentrations in proliferative diabetic retinopathy (PDR) and controls (macular hole, epiretinal membrane, symptomatic vitreous floaters) from pars plana vitrectomy.
RESULTS
An adequate volume of vitreous fluid (100-200 μL) was obtained in 52 (88%) of 59 office-based sampling attempts. The average length of follow-up was 300 days (range, 42-926 days). There were no complications, including cataract, retinal tear or detachment, and endophthalmitis. Two patients (3%) had posterior vitreous detachments within 3 months. Vitreous cytokine concentrations were measured in 44 patients: 14 controls, 13 with DME, and 17 with PDR. The concentration of ADAM11, CXCL-10, IL-8, and PDGF-A were higher in PDR compared with controls and DME. The concentration of IL-6 was higher in PDR compared with controls, but not compared with DME.
CONCLUSIONS
Office-based vitreous aspiration is safe and yields high-quality samples for multiplex vitreous cytokine analysis. Significant elevations of vitreous cytokines were found in PDR compared with DME and controls, including the novel finding of elevated ADAM11. As such, office-based aspiration is a safe and effective means to identify vitreous factors associated with vitreoretinal disease.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biopsy, Fine-Needle; Case-Control Studies; Child; Cytokines; Diabetic Retinopathy; Diagnostic Techniques, Ophthalmological; Female; Humans; Macular Edema; Male; Middle Aged; Postoperative Complications; Prospective Studies; Safety; Vitreous Body; Young Adult
PubMed: 27273720
DOI: 10.1167/iovs.15-18721 -
Asia-Pacific Journal of Ophthalmology... 2016This study aimed to objectively grade the perception of subclinical floaters in an asymptomatic cohort. (Observational Study)
Observational Study
PURPOSE
This study aimed to objectively grade the perception of subclinical floaters in an asymptomatic cohort.
DESIGN
A prospective observational cohort study.
METHODS
One hundred eighty-two volunteers (49 men, 133 women) with ages ranging from 17.7 to 78.6 years were recruited for floater assessment. Participants were assessed by a light box and by vitreoscope, after which they graded the floaters using a graphic classification system. They also completed a questionnaire to estimate the impact of floaters on daily life. In addition, biometric and refractive data were documented for all participants.
RESULTS
Using the light box method, 67.6% of participants reported seeing transparent floaters, which increased to 84.1% when using the vitreoscope. Opaque floaters were seen by 15.9% (light box) and 6.5% (vitreoscope). Reported levels of floater discomfort varied between participants, with 80.2% of participants reporting no discomfort and 6.6% reporting moderate to manifest discomfort. The perceived discomfort was weakly correlated with the amount of visualized floaters (light box: Pearson r = 0.323, P < 0.001; vitreoscope: r = 0.174, P < 0.001). Both floater perception and discomfort increased with age (r = 0.203, P = 0.006; r = 0.194, P = 0.009, respectively), although neither changed with axial length or refraction (P = 0.131, P = 0.070, respectively).
CONCLUSIONS
The light box and the vitreoscope demonstrate that subclinical floaters are very common, even in nonsymptomatic subjects. The amount of perceived floaters in this cohort correlates only weakly with floater-related discomfort.
Topics: Adolescent; Adult; Age Factors; Aged; Eye Diseases; Female; Humans; Male; Middle Aged; Prospective Studies; Refraction, Ocular; Surveys and Questionnaires; Visual Acuity; Vitreous Body; Young Adult
PubMed: 26918903
DOI: 10.1097/APO.0000000000000189