Is there anything measured for eyes?

What this archive is for. Trials of the compound come first, ranked by how many people were actually given it. Studies that only observed people are below them and labelled.

1. 01Thymosin Beta-4PeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 5 completed trials, 1,382 people given it.9 reported

   1,382 people given it4 trials

   • The biggest trial of these eye drops came out flat as well. Seven hundred people with dry eye used the drops or a dummy solution, and after two weeks both groups had improved by the same amount. Everybody getting better together is what you see when the improvement is not coming from the drug. A trial this size would have shown a real difference if one existed.

     The numbers 700 patients. Registry-posted primary results at day 15: inferior corneal staining minus 0.41 on drug against minus 0.46 on placebo, ocular discomfort minus 0.4 on both arms. The two groups moved together.

     ClinicalTrials.gov, ReGenTree, LLC, 2021· 700 people

   • A large trial of thymosin beta 4 eye drops found nothing. It gave 601 people with dry eye either the drops or an identical dummy solution. A month in, eye discomfort and the staining that shows surface damage were no better on the drug. On discomfort the drug group was fractionally worse. This is one of the two biggest tests this peptide has ever been given, and it came out flat.

     The numbers 601 patients, 0.1% RGN-259 against placebo. Registry-posted primary results at day 29: ocular discomfort plus 0.07 versus minus 0.04, corneal fluorescein staining plus 0.07 versus minus 0.01, on scales where higher is worse.

     ClinicalTrials.gov, ReGenTree, LLC, 2018· 601 people

   • The main measures in this small trial came out even. Seventy two people with dry eye used the drops or a dummy solution for four weeks, and neither of the two things the trial was built to measure separated. In a chamber where the air was dried out deliberately, the drug group reported less discomfort, and staining in parts of the cornea improved. Those were extra measures, not the test the trial had set itself.

     The numbers 72 subjects randomized 1:1 for 28 days: neither primary endpoint separated from placebo. Secondary endpoints showed 27% lower discomfort during the chamber challenge (p = 0.0244) and improved central and superior corneal staining.

     Clinical Ophthalmology, 2015· 72 people

   • Eye drops helped severe dry eye in a study of nine people, which is far too few to rely on. Patients used either the thymosin beta 4 drops or drops without it, and nobody involved knew which. After eight weeks, discomfort was down 35% and damage to the surface of the eye down 59% compared with the plain drops. Nine patients is a handful. These are drops on the eye, not an injection, so they say nothing about the injectable peptide sold online.

     The numbers Small placebo-controlled Phase 2 (9 patients): RGN-259 eye drops cut ocular discomfort 35% and corneal staining 59% versus vehicle at day 56.

     Cornea, 2015· 9 people

2. 02PegcetacoplanPeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 3 completed trials, 1,258 people given it.3 reported

   1,258 people given it1 trial

   • The eye injection slowed the damaged area from spreading and did nothing for anyone's sight. 1,258 people aged 60 and over took part in two identical trials, one of which hit its one year target and one of which missed. By two years both showed the damage growing roughly a fifth more slowly on treatment. Vision itself was no better. Treatment also triggered the wet form of the disease far more often, in roughly one in ten against one in fifty. Funded by Apellis.

     The numbers 1258 patients aged 60 and over. At 12 months OAKS met its primary endpoint, with lesion growth slowed 21 percent monthly (P equal to 0.0004) and 16 percent every other month (P equal to 0.0055), while DERBY missed it, at 12 percent (P equal to 0.062) and 11 percent (P equal to 0.085). By 24 months both were significant, 22 and 18 percent in OAKS and 19 and 16 percent in DERBY. The paper states there were no differences in key secondary visual function endpoints at 24 months. New-onset exudative age-related macular degeneration at 24 months: 11 and 8 percent on pegcetacoplan versus 2 percent on sham in OAKS, and 13 and 6 percent versus 4 percent in DERBY. Funded by Apellis Pharmaceuticals.

     The Lancet, 2023· 1,258 people

3. 03RisuteganibPeptideModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 263 people given it.

   218 people given it1 trial, 1 watch-only

   • Put head to head against a standard eye drug, this one came off worse. Two hundred and eighteen people with swelling in the retina from diabetes were split across nine groups. After six months, sight had improved most in the group given the standard drug. The best risuteganib dose did less, and the highest dose left people slightly worse than when they started. The company posted the figures but never compared them formally and never published a paper. The company paid.

     The numbers 218 participants with DME across nine arms. Posted results (December 2018): mean change in best corrected visual acuity at week 24 of +5.2 letters (1.0 mg), +2.7 (2.0 mg) and -1.5 (3.0 mg) with risuteganib, versus +7.0 with bevacizumab. No statistical comparison posted and no journal publication located. Sponsor funded.

     ClinicalTrials.gov, Allegro Ophthalmics, 2014· 218 people

   • This is a second look at the same thirty nine people, done after the trial ended. It asked which eyes had improved, and the answer was the eyes in better shape to begin with. Those with more surviving retina gained the most lines on the chart. The authors suggest picking patients like this for future trials. Looking for patterns after the results are in can turn up almost anything. Treat this as a hint, not a finding. Public money paid for the analysis.

     The numbers Post hoc analysis of the 39 completers of the phase 2a. Eyes with more intact ellipsoid zone, thicker outer retina and less geographic atrophy at baseline were more likely to gain 8 letters. Exploratory, and proposed by the authors as a way to enrich future trials. NIH supported analysis.

     Ophthalmology Retina, 2022· number of people not givenobserved only, nobody was given it

4. 04ARA-290PeptideLimited. People have taken it in a published study, but fewer than 100 of them. 5 completed trials, 95 people given it.7 reported

   73 people given it4 trials

   • The larger trial showed a change in the nerves and failed to show a change in the pain. Sixty-four patients with sarcoidosis took 4 mg a day or a dummy injection. The area of tiny nerve fibres in the cornea grew on the drug. But pain got better in every group, including the dummy one, so there is no way to tell the drug apart from expectation on the thing patients actually care about. That is the result, and it is a disappointment.

     The numbers Phase 2b in 64 patients: 4 mg/day cibinetide significantly increased corneal nerve fiber area versus placebo; pain improved in all groups, so the pain effect was not clearly separated from placebo.

     Investigative Ophthalmology and Visual Science, 2017· 64 people

   • Every objective measure in this small trial stayed flat. Nine people with swelling at the centre of the retina injected cibinetide daily for three months, and eight finished. Their vision did not improve. Neither did retinal thickness, retinal sensitivity or tear production. The only thing that rose was how they rated their own sight on a questionnaire. Four of the authors are officers and shareholders in the company that owns the drug. Nine people cannot settle the question either way.

     The numbers 9 patients recruited and 8 completed 12 weeks at 4 mg per day: no improvement in visual acuity, central retinal thickness, retinal sensitivity or tear production. Only the vision-related quality of life composite moved. Four authors are officers and shareholders of the sponsor.

     Journal of Clinical Medicine, 2020· 9 people

   • A month of daily shots improved nerve symptoms and, for once, changed something a machine could see. Patients with sarcoidosis and nerve fibre loss injected ARA 290 or a dummy under the skin for 28 days, and nobody involved knew which. Symptoms improved, and the density of tiny nerve fibres in the cornea went up. That second measure matters because it does not depend on how anyone feels. This was still a short study in a small group with one uncommon disease.

     The numbers 28 days of daily subcutaneous ARA 290 improved neuropathic symptoms and increased corneal small nerve fiber density in a blinded placebo-controlled trial.

     Molecular Medicine, 2013· number of people not given

   • People with diabetes and painful nerve damage injected ARA-290 daily for a month, and several measures moved. Average blood sugar and blood fats improved over two months of watching, and people reported less nerve pain. Nerve fibres in the eye increased only in those who started well below normal. The published summary never says how many people took part, which makes the result impossible to weigh. Nobody has repeated it.

     The numbers 28 days of 4 mg per day self-administered subcutaneously in type 2 diabetes with painful neuropathy: improved HbA1c and lipids over 56 days of observation and improved PainDetect scores. Corneal nerve fiber density rose only in subjects starting more than 1 SD below normal. The abstract does not state the number randomized.

     Molecular Medicine, 2015· number of people not given

5. 05GLOW blendBlendLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, 22 people given it.9 reported

   9 people given it1 trial

   • The parent protein helped severe dry eye, in nine people, as an eye drop. Some got drops with it and some got the same drops without it. After eight weeks the treated eyes were more comfortable, and the damage on the surface of the eye had more than halved. Nine people is very few. And this was an eye drop of the full protein, not the fragment sold in a vial for injection.

     The numbers A 9 patient multicentre randomised double-masked placebo-controlled phase 2 trial of thymosin beta 4 eye drops in severe dry eye. At day 56 the treated group showed a 35.1% reduction in ocular discomfort and a 59.1% reduction in total corneal fluorescein staining against vehicle. This is the parent protein, as an eye drop, in nine people. It is included because it is the human evidence usually implied for the TB-500 in this vial, and it is not about that molecule or that route.

     Cornea, 2015· 9 people

Vitamins, minerals, amino acids and botanicals sold over the counter, held to the same standard.

1. 01IdebenoneSupplementModerate. At least one finished study in people, and at least 100 people who took it. 5 completed trials, 732 people given it.

   85 people given it1 trial

   • Idebenone failed the main question in this trial, and the approval rests on what came afterwards. 85 people with an inherited cause of sudden blindness took a high daily dose or a dummy for 24 weeks, and nobody involved knew which. Best recovery of vision, the thing the trial was built to measure, was not clearly better on the drug. A later reanalysis found differences in people whose two eyes were affected unequally, but that analysis was devised after the results were in. The drug was tolerated well.

     The numbers RHODOS. 85 patients with m.3460G>A, m.11778G>A or m.14484T>C mutations, idebenone 900 mg a day for 24 weeks, multicentre, double blind, placebo controlled. The primary endpoint, best recovery in visual acuity, did not reach statistical significance in the intention to treat population. A post hoc interaction analysis found significant secondary endpoint differences in patients with discordant visual acuities at baseline. Idebenone was safe and well tolerated.

     Brain, 2011· 85 people

Peptides and blends

1. 01SHLP2PeptidePreliminary. Studied in people, but no published study has had people take it. 2 human studies where nobody was given it.6 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In a dish. Cells from the back of the eye, the kind that fail in age-related vision loss, were protected from oxygen damage. The eye claims made for this peptide go back to work at this level. No patient was involved.

     The numbers Retinal pigment epithelium cell work relevant to age-related macular degeneration, reporting protective effects against oxidant injury. Cell culture. The eye claim that circulates for this peptide traces to work at this level, not to any patient.

     Scientific Reports, 2018· lab (cells in a dish)

Supplements

1. 01Procyanidin C1SupplementAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 2 animal studies, no human study.2 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In old mice. Long-term treatment cut worn-out cells in the eye and eased age-related decline in how the eye is built and works. Mouse only, and it did not look at lifespan.

     The numbers Naturally aged mice. Long-term procyanidin C1 treatment reduced retinal senescent cell burden and ameliorated age-related structural and functional decline in the retina, characterised by single-cell RNA sequencing. Mouse, no lifespan endpoint.

     Proceedings of the National Academy of Sciences, 2024· animal study

Other compounds

1. 01OSK Partial ReprogrammingBiologicPreliminary. Studied in people, but no published study has had people take it. 1 registered with no result.5 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In mice, switching on three of the Yamanaka genes in the nerve cells at the back of the eye made those cells look younger. The chemical tags on their DNA went back to a young pattern. Damaged optic nerves regrew. Sight came back in mice with glaucoma and in old mice. The benefit needed two enzymes, TET1 and TET2, which strip those tags off. Funded by the US National Institutes of Health with other support.

     The numbers Mouse. Ectopic expression of Oct4, Sox2 and Klf4 in mouse retinal ganglion cells restored youthful DNA methylation patterns and transcriptomes, promoted axon regeneration after optic nerve injury, and reversed vision loss in a mouse glaucoma model and in aged mice. The benefit required the DNA demethylases TET1 and TET2. NIH funded, with non-US government and non-PHS support.

     Nature, 2020· animal study