Blood Derived Therapies in Refractory Ocular Surface Disease

Transcription

1 Blood Derived Therapies in Refractory Ocular Surface Disease John E. Conto, OD, FAAO, ABCMO Assistant Professor of Ophthalmology and Visual Science Please silence all mobile devices and remove items from chairs so others can sit. Unauthorized recording of this session is prohibited.

2 Financial Disclosure Statement: None

3 Lecture Objectives What typical ocular surface conditions are blood-derived therapies (BTD) used? How are BDT used in stepped therapy? What does the review literature suggest about the use of BDT? How available are BDT? What are the risks of the use of BDT?

4 Perspective Katzan HM. Aqueous fibrin fixation of corneal transplants in the rabbit Arch Ophthalmol 1946;35: Ralph RA, Doane MG, Dohlman CH. Clinical experience with a mobile ocular perfusion pump. Arch Ophthalmol. 1975;93: Fox RI, Chan R, Michelson JB, et al. Beneficial effect of artificial tears made with autologous serum in patients with keratoconjunctivitis sicca. Arthritis Rheum 1984;27: patients, age 20-88, all female 8 with Sjögren s Syndrome 11 patients remained in study and showed marked improvement in signs and symptoms.

5 Perspective 120 ASD Publications #Articles

6 Perspective

7 Indications for BDT Aqueous deficient OSD Filamentary keratitis Exposure keratitis Ocular GVHD Ocular cicatricial pemphigoid Persistent epithelial defects Recurrent corneal erosion Neurotropic keratopathy Limbal stem cell deficiency Intolerant to other therapies Ocular neuropathic pain ( pain without stain ) Ophthalmic Atlas Images courtesy of University of Iowa

8 BDT and Adjunctive Therapy Non-preserved artificial tears and gels Punctum plugs Topical anti-inflammatory agents Amniotic membranes (PROKERA, AmbioDisk ) Bandage or scleral lenses Environmental controls (moisture goggles, humidifiers)

9 Autologous serum (ASD) Allogeneic serum (AGSD) Finger prick Autologous blood (FABD) Platelet rich plasma (E-PRP or PRGF) Human albumin (HAD) Umbilical cord serum (UCS) BDT Types

10 Autologous Serum Drops Closest natural tear supplement available Biomechanical qualities lubrication Hydration Similar biochemistry ph Osmolarity Albumin Epithelial growth factor Transforming growth factor- β1 Vitamin A Lysozyme Surface Immunoglobulin A Fibronectin and cytokines G Quinto, M Campos, A Behrens. Arq Bras Oftalmol. 2008; 71(6 Supl):47-54

11 ASD Typical Procedure 1. Blood Draw 2. Centrifuge 3. Serum Collection 4. Packaging

12 ASD Production Differences Surveyed 12 countries and 55 institutions regarding production of ASD/AGSD with 40% making drops 71% ASD, 10% AGSD and 19% both Concentration: 38% produce 20% 15% produce 20-30% 31% produce 30-50% Frozen shelf life 33%, 3-4 months 14%, 6 months 24%, 12 months Thawed shelf life 52%, 24 hours 5%, 48 hours 10%, 1 week

13 ASD Production Differences

14 ASD Review Review of publication indexes (thru July 2016) Compared ASD versus artificial tears, random controlled studies (n=92) Found major differences in endpoints and data reporting Maybe short term benefit, but did not demonstrated long term versus artificial tears Need to have well-planned, large high quality RCT to determine effectiveness.

15 ASD Citations Retrospective cohort with 50% ASD 123 eyes Ocular surface evaluation up to six months after initiating ASD NaFl staining improved by 3-6 month F/U Schirmer scores improved to mean of 11 mm by month F/U OSDI scores improved to from mean of 54 to 39 by 12 month F/U No complications seen

16 ASD Citations 24 patients with SSDE followed for six months Compared ASD versus artificial tears OSDI scores significantly lower in ASD group Shirmers, TBUT and NaFl staining no difference Confocal changes demonstrated fewer beadlike formations and sub-basal nerve branches

17 Efficacy and Safety of ASD Comparison to first line therapies 50% decrease in OSDI versus 20% with other therapies In PED, 60-90% healed within 25 days Complications Risk of contamination/infection increases with concentration Immunoglobulin deposition in corneal stroma

18 Availability and Costs legality and informed consent non-fda approved within scope of provider given established therapy varies between states suggest FAQ patient guide protocol blood draw by licensed blood processing laboratory serology testing for hepatitis B, C and HIV-1, 2 and syphilis prepared by compounding pharmacy in % concentration typical batch of 3 month supply in single use 2 ml or 5 ml vials application kept frozen until use (3-6 months) typical dosage 1-2 drop QID costs varies between $75-150/month USD rarely covered by insurance

19 Recurrent Erosions Before ASD 20% ASD 6 weeks

20 Ocular GVHD Before ASD 50% ASD 8 weeks

21 Before ASD & 20% ASD 12 weeks Ocular Neuralgia

22 Allogeneic ABO-Specific Serum Used when autologous serum contraindicated Infants Elderly Patients with blood infectious disease Patients with harmful drug metabolites Matched by type A, B, AB and O Male donors only to avoid HLA and leucocytespecific antibodies to avoid possible immune complex-mediated inflammation Preparation similar to ASD Banked and easily prescribed Efficacy similar to ASD

23 Autologous Blood Drops (Fingerprick) Limited case series Lancet prick and place drop of blood in lower culde-sac, QID for 8 weeks Significant statistical improvement in corneal staining, visual acuity, TBUT and OCI score No change in Schirmer s test When therapy stopped, all the above worsened.

24 Platelet Rich Plasma (PRP) (Plasma Rich in Growth Factors (PRGF) Mechanism of action same as ASD Higher concentration of growth factors (EGF and TGF-ß1 Tightens the epithelial adhesion complex

25 PRGF Efficacy PRGF as monotherapy 368 patients with moderate to severe DED 63% EDED, 37% ADDE After 6 weeks of therapy: Symptoms (OSDI) improved in 88% NaFl staining (Oxford) decrease in 76% of cases Improvement in one line acuity in 29%

26 BTI technology Endoret (PRGF ) Indications moderate to severe dry eye persistent epithelial defects corrective amyotrophia surgery burns, perforations, inflammation Four formulations suturable fibrin membrane liquid plasma clot enriched with growth factors eye drops

27 PRGF Citations

28 Human Albumin (HAEDS) Tear supplement that allows to retain moisture and drug contact time Suppresses apoptosis of conjunctival and cornea cells Has antioxidant and anti-inflammatory properties Commercially available as 5% typically is used About $50 USD/month

29 Human Albumin (HAEDS)

30 Human Albumin (HAEDS) VS. Hyaluronan 0.1% RECURRENCE % PED CU 5% A LBUMIN 0.1% HYALURONA N

31 Umbilical Cord Serum (UCS) Derived from umbilical cords of consenting mothers. Diluted to 20% concentration. Minimal adverse effects on the eye because of reduced immunogenicity. Titers of IgM and IgG antibodies are low and anti-a and anti-b antibodies are absent or only weakly detectable in the serum.

32 Umbilical Cord Serum (UCS) Initial 7 days 14 days

33 Amniotic Membrane Extract (AMEED)

34 Amniotic Membrane Extract (AMEED)

35 Amniotic Membrane Extract (AMEED)

36

37 BDT Considerations Useful adjunct in advanced ocular surface disease Safe, with minimal complications Compounding varies considerably with ASD Increasingly available and cost effective

38 Thank You!

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