Scleral Lenses as a Drug Delivery Modality:

Pros and Cons

Lynette K. Johns, OD, FAAO, FSLS, FBCLA

Research Associate
Harvard Medical School Department of Ophthalmology
 Disclosures
• Nothing to Disclose

Massachusetts Eye and Ear / Harvard Ophthalmology

 The Fluid Reservoir

Massachusetts Eye and Ear / Harvard Ophthalmology

 Tear Exchange

• Fastest exchange rate: 840 µl/hour

• Slowest: 20 µl/hour
• In channeled scleral lenses with
fluorophotometry

• One third had out-in time ≥ 5 minute

• Inflow rate average: 0.4 ± 0.9%/min

• “The relationship between the amount of
tear exchange during scleral lens wear and
• Tear flow in occurred at 20 min and 5 h
the incidence of MDF was not significant.”
• 60% had out-in time < 5 min after 5 hours
• After 5 h one third of the subjects had no
tear flow assessed with fluorogram

Massachusetts Eye and Ear / Harvard Ophthalmology

 Tear Exchange is Dependent on Fit

Spherical Periphery Toric Periphery

Massachusetts Eye and Ear / Harvard Ophthalmology
 Preservative Toxicity

Caroline P, Andre M. Preservative Toxicity while Wearing Scleral Lenses.

CLSpectrum, Volume: 29, Issue: November 2014, page(s): 56
Massachusetts Eye and Ear / Harvard Ophthalmology
 Topical Ophthalmic Medications
• Most of the ocular medication is lost to drainage after 15-30
seconds Shell JW: Pharmacokinetics of topically applied ophthalmic drugs. Surv Ophthalmol
26:207–18, 1982

• The tear turnover rate is approximately 16%/minute

• All the drug should disappear within 10 minutes after dosing
• Instilled drug is diluted to about 1/3 of original drop Maurice D,
Mishima S:Ocular pharmacokinetics. in SearsML(ed): Pharmacology of the Eye. New York, Springer-
Verlag,1984, pp 19–116

Massachusetts Eye and Ear / Harvard Ophthalmology

 Solution Additives

Preservatives Solubilizing/Stabilizing Agents

• Thimerosal • macrogolgly-cerol hydroxystearate
• Edetate Disodium (MGHS40)
• Benzalkonium Chloride • Polysorbate 80 (PS80)- nonionic
• Chlorhexidine surfactant and emulsifier
• Polyquad
• Chlorobutanol
• Phenylmercuric Nitrate
• Polyaminopropyl Biguanide
• Benzyl Alcohol
• Polixetonium Chloride

Massachusetts Eye and Ear / Harvard Ophthalmology

 Benzalkonium Chloride
• Present in 70% of topical solutions

10 min

10 min exposure BAK

30 min

Hakkarainen J. et al. Acute cytotoxic effects of marketd ophthalmic formulations on human corneal
epithelial cells. International Journal of Pharmaceutics 511 (2016) 73–78

Massachusetts Eye and Ear / Harvard Ophthalmology

Additives in Preservative-Free Formulations

10 min 30 min

Massachusetts Eye and Ear / Harvard Ophthalmology

 Management of Persistent Epithelial Defects
• Retrospective review 14 eyes/13 patients
• 7 eyes (SJS)
• 12 eyes post-PKP
• Extended wear of lenses
• 8 resurfaced (5 SJS)
• MK occurred in 4 eyes

• Rosenthal et al. Treatment of Persistent

Corneal Epithelial Defect With Extended
Wear of a Fluid ventilated Gas-permeable
Scleral Contact LensAm J Ophthalmol
2000;130:33–41.

Massachusetts Eye and Ear / Harvard Ophthalmology

 Management of Persistent Epithelial Defects
• Retrospective interventional case series 20 eyes/19 patients
• 7 eyes (GVHD)
• 5 eyes (NK)
• 4 eyes (LSCD)
• 2 eyes (SJS)
• 1 eye (KCS)
• 1 eye (ectodermal dysplasia)
• Extended wear of lenses
• Healing times
• <7 days in 12 eyes
• 8-14 days in 2 eyes
• >14 days in 3 eyes
• (range: 1-43 days)
• No MK
• Moxifloxacin used in all cases

• Lim P, et al. Treatment of Persistent Corneal Epithelial Defect With Overnight Wear of a Prosthetic Device for the Ocular
Surface. AJO 2013. 1094-1101.

Massachusetts Eye and Ear / Harvard Ophthalmology

 Moxifloxacin
• Fourth generation fluoroquinolone
• Preservative-free/Self-preserved
• Subjected to the Antimicrobial Preservative Efficacy Test required in
the United States Pharmacopoeia (USP)
• Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia
coli, Candida albicans, Aspergillus niger were all reduced to acceptable
levels after gross contamination of the product.
• In addition, challenges with the protozoan, Acanthamoeba, and two other
fungi, Nocardia and Fusarium, also show killing after inoculation.
Schelch et al., Antimicrobial Preservative Effectiveness of Vigamox. Investigative Ophthalmology & Visual Science
May 2004, Vol.45, 4913. abstract

Massachusetts Eye and Ear / Harvard Ophthalmology

Management of Persistent Epithelial Defects

• 3 eyes/3 patients re-epithelialized

• No MK
• ASD in lenses
• Average healing 14.3 days

• 3 different scleral lens designs

• 8/8 re-epithelialized
• ASD in some cases
• Amnion in some cases
• No MK
• Average healing 11 days

Massachusetts Eye and Ear / Harvard Ophthalmology

 15
Management of Persistent Epithelial Defects
• Photography white light and cobalt filter if available
• Extended wear of scleral device
• Daily monitoring
• Antibiotic prophylaxis (preservative-free)
• Daily disinfection of device and replenishment of fluid
• Longstanding PED’s can be managed with exchange of 2 devices q12 hours
• Weekend monitoring
• DOCUMENTATION!!!!!!

Massachusetts Eye and Ear / Harvard Ophthalmology

Case 1: Persistent Epithelial Defect

Day 1 Day 2

Day 3 Day 5
Massachusetts Eye and Ear / Harvard Ophthalmology
Case 2: Persistent Epithelial Defect

Day 1 Day 3

Day 7 Day 10
Massachusetts Eye and Ear / Harvard Ophthalmology
Problems with Extended Wear

Massachusetts Eye and Ear / Harvard Ophthalmology

When a PED doesn’t heal…

Massachusetts Eye and Ear / Harvard Ophthalmology

 Anti-Angiogenesis
• Topical corticosteroids
• Nonsteroidal anti-inflammatory agents
• Cryotherapy
• Photodynamic therapy with a photosensitizer
• verteporfin
• Fine needle diathermy
• Subconjunctival injection of Bevacizumab

Massachusetts Eye and Ear / Harvard Ophthalmology

 Bevacizumab
• Recombinant, humanized, monocolonal antibody
• Binds to and deactivates VEGF
• FDA approved in 2004 treatment for patients with metastatic colorectal cancer
• Intravitreal injections for wet age-related macular degeneration
• Topical treatment of corneal neovascularization
• Reduction in active neovascularization
• Improved comfort in patients with Stevens-Johnson syndrome
• Adverse events
• Epitheliopathy
• Stromal thinning

Massachusetts Eye and Ear / Harvard Ophthalmology

 Anti-VEGF
Figure 2

b c d
Keating A., Jacobs D. Anti-VEGF Treatment of Corneal Neovascularization. The
Ocular Surface. 2011 9 (4): 40-51.
 Case 3: Persistent Epithelial Defect with
Neovascularization
• 61 y.o. F referred for resurfacing PED 1 month s/p patch for perforation
• 3 eye surgeries in prior 6m
• s/p Phaco CE, PCIOL
• s/p PPV/AFx/EL/16% C3F8
• s/p PK Patch graft for descemetocele
• Secondary Sjögren’s syndrome
• Neurotrophic cornea
• ? Stem cell deficient

Massachusetts Eye and Ear / Harvard Ophthalmology

 Case 3
Entering Treatment by specialist :
Vigamox QID
PF Pred Forte BID
Serum Tears q2h
Doxy 50 mg p.o QD
Bandage CL
 Case 3

Re-surfaced after 6 days continuous wear and Vigamox in the device

Massachusetts Eye and Ear / Harvard Ophthalmology
 Case 3

October 2007 March 2008

VA: CF 6’ VA: 20/400 6/120 0.05
1w after continuous then daily s/p 3 months topical Avastin in lens,
wear suture removal, systemic steroid.
?PK for vision
Massachusetts Eye and Ear / Harvard Ophthalmology
 Case 3: 3 years later…

July 2011 •Overnight wear with lens and one

s/p PKP January 2011 drop Vigamox.
VA: 20/50 6/15 0.40 •Resurfaced in 24 hours
Massachusetts Eye and Ear / Harvard Ophthalmology
Animal Studies: Drug Delivery with Scleral Lenses

• Labelle R. et al. Cont Lens Anterior Eye. 2016

Oct;39(5):394-6
• n = 4 rabbits; ICD 16.5 diameter; clearance 300 microns;
0.3% Ofloxacin
• Corneal and Aqueous humor concentration greater than
minimum inhibitory concentration

Massachusetts Eye and Ear / Harvard Ophthalmology

 Animal Studies: Stem Cell Delivery

• 11 rabbits with alkaline burns

• 1 –No treatmentà Melted with symblepharon
• 5 –EW scleral lensesà No symblepharon
• 5 –EW scleral lenses with human stem cellà No symblepharon, less neo, less opacity

Massachusetts Eye and Ear / Harvard Ophthalmology

 Summary
Pros
• Drug delivery is possbile in a scleral
lens
• Use of preservative-free antibiotics
reduce MK in extended wear PED
resurfacing
• Anecdotal use of anti-VEGF agent
reduces corneal neo with drug
delivery in a scleral lens
• May be possible to deliver stem
cells to LSCD eyes
Massachusetts Eye and Ear / Harvard Ophthalmology
Cons
• Not enough data on the
concentration of the drug in the
reservoir
• Additives may contribute to
cytotoxicity for prolonged periods
of time—needs further
investigation
• Anterior chamber levels of drug are
unknown without further
investigation
• Proceed with caution!
 Thank You!
Lynette_Johns@meei.Harvard.edu
Yin, J. and Jacobs, D.S. (2019) Long-term outcome of using Prosthetic Replacement
of Ocular Surface Ecosystem (PROSE) as a drug delivery system for bevacizumab in
the treatment of corneal neovascularization. The Ocul Surf, 17, 134-141.
 8 wks – decrease to QOD until
s/p 1 wk BID 4 wks – decrease to QD completion of med

Yin, J. and Jacobs, D.S. (2019) Long-term outcome of using Prosthetic Replacement
of Ocular Surface Ecosystem (PROSE) as a drug delivery system for bevacizumab in
the treatment of corneal neovascularization. The Ocul Surf, 17, 134-141.