Transcript Adjunctive Autologous Serum Tears in High

Adjunctive Autologous Serum
Tears in High-Risk Penetrating
Keratoplasty
Erich B. Groos, Jr., M.D.
Cornea Consultants of Nashville
The author has no financial interest in the subject
matter of this poster.
Introduction
 Penetrating keratoplasty (PK) in the setting of corneal epithelial
healing abnormalities is high risk for persistent defects and
infectious keratitis.
 Diagnoses such as neurotrophic keratitis and limbal stem cell
deficiency (LSCD) render re-epitheliazation times slow to nonexistent depending on the severity of the disease.
 Controlling lubrication and managing exposure to the toxic effects of
lid margin bacteria and topical mediations has limited effectiveness.
 Amniotic membrane transplantation and lateral tarsorrhaphy have
been used previously to provide early (AMT) or ongoing (LT)
protection of the epithelium during healing.
 This poster displays results of the use of 20% autologous serum
tears (AST) in the perioperative and ongoing management of PK in
eyes with impaired corneal epithelial healing.
 This study is a historical case series.
 The use of autologous serum tears in this manner and setting is not
an FDA-approved treatment modality.
Methods
 A series of 10 patients were enrolled after extensive discussion of risks and benefits
of surgery. Particular attention was given to the high risk nature of keratoplasty in the
setting of their particular disease states.
 Surgery was performed by one surgeon (EBG) using 16 interrupted 10-0 nylon
sutures. Subconjunctival dexamethasone and cephazolin were used along with
Healon over the graft and tobramycin/dexamethasone (Tobradex) ointment on the lids
prior to patching.
 On the first postoperative day, all patients (except patient #10) were started on
preservative-free 20% mixtures of autologous serum, prepared by the same
pharmacy (Health and Wellness Pharmacy, Nashville, TN) in a sterile and consistent
manner, q2hours while awake beginning on the first postoperative day. Vials were
frozen until use and discarded after 4 days of use or sooner.
 Topical preservative-free dexamethasone (0.1%) was used in place of commercial
steroids and initially at q2 hours while awake.
 Whenever possible, topical antibiotics (Vigamox/moxifloxacin) and glaucoma
medications were chosen for either reduced frequency of application or the lack of a
preservative.
 The patients were seen at one day, one week and then every 2-6 weeks thereafter
depending on their early course, presence or absence of complications and severity
of preoperative corneal condition.
 Endpoints of note were intact epithelium, degree of epitheliopathy, clarity of graft and
visual acuity.
Results-Preoperative Patient Demographics
 Age: Range - 37 to 85, Average - 67.6, Median 67 years.
 Sex: 4 Male/6 Female.
 Diagnosis: 10/10 with impaired corneal sensation from LSCD (1),
HZV (5), presumed HZV (2), and HSV (2). 5/10 with
preoperative neovascularization in at least one quadrant.
 Visual Acuity: Range from 20/100 to LP, with 7/10 CF or worse.
 Non-healing defects: 4/10 had hx of delayed healing of epithelial
defects, 2 leading to AMT transplants and one requiring AST. 2
of these were following superficial keratectomies.
 Previous Perforations: 3/10 had immediate preoperative
perforations (HZV, Bipolaris ulcer, serratia marcescens ulcer),
and another prior to a previous graft (fusarium ulcer).
 Previous surgeries: 7/10 pseudophakic at time of transplant,
2/10 with previous PK, 1/10 with 3 PK’s-DSAEK-Ahmed Implant,
and 2/10 with AMT.
Results-Postoperative Course
 Duration of Follow-up: Range from 7 to 42, Average 22.5, Median 18.5
months.
 Epithelial Healing Interval Post-op: 9/10 less than a week with one less
than 2 weeks.
 Graft Clarity: 8/10 clear at last follow-up, 1/10 with chronic KP from uveitis
(2nd PK, Fusarium, perforation) and 1/10 with vascularization and
peripheral stromal scar from allograft rejection.
 Epithelial Health: 9/10 with clear, smooth epithelium at last follow-up.
 Visual Acuity: 7/10 BSCVA 20/40 or better. Range 20/20 to 20/200 (20/60 only 7 months follow-up, 20/80 - 5 previous procedures and one
subsequent, 20/200 - chronic uveitis secondary to perforated fusarium ulcer
and one previous PK).
 Adverse events: 5/10 with persistent mixed mechanism glaucoma, 5/10
with cataract extraction (2 classic triples), one reposition of lens implant,
one multiple YAG removal of inflammatory membranes from IOL.
 Allograft Rejections: 1/10 resolved dramatically after hospitalization for
systemic steroids to treat acute bronchial asthma.
 Ongoing Treatment: 7/10 require AST as of their last follow-up. 0/10
require ongoing preservative-free drops (steroids, hypotensives).
Case Detail - Patient #6
 62 YO female with history of ophthalmic herpes zoster on the left in
2003.
 7/14/2008 - Visual Acuity 20/100-, corneal stromal scarring, thinning
and vascularization. Decreased corneal sensation and cataract.
 10/8/2008 - PK with ECCE and IOL. Patch overnight, Healon on
cornea, tobramycin dexamethasone (Tobradex) ung on lids.
 10/9/2008 - Starts AST 20% and PF dexamethasone (0.1%) q2h
while awake, moxifloxacin (Vigamox) qid.
 10/16/2008 - Graft thin and clear with intact epithelium and no vortex
keratopathy.
 8/18/2009 - BSCVA - 20/20. Graft thin and clear. Fluoromethalone
(FML) bid, timolol hemihydrate 0.5% (Betimol) qd and AST qid.
 1/19/2010 - BSCVA 20/20. FML bid and AST qid.
 18 months follow-up.
 Preop Photo Next Slide.
Preop Photo - Patient # 6
Case Detail - Patient #3
 74 yo female with history of Fuchs’ OU presents 12/2/2002 with bullous
keratopathy and KP OS, responds to topical steroids and vision improves from
20/100 to 20/70. Pertinent medical history + for polymyalgia rheumatica and on
oral steroids.
 12/2003 Phaco with IOL OS uncomplicated.
 5/5/2004 OS develops geographic ulcer and melt off steroids for 4 days.
 6/1/2004 undergoes AMT multilayer inlay in 90% non-healing defect with AMT
overlay as well.
 10/25/2006 undergoes PK OS with usual postoperative regimen as discussed in
methods.
 10/26/2006 - 50% epithelial defect. Starts AST, Vigamox and PF
dexamethasone.
 10/31/2006 - Epithelium intact
 9/15/2009 - 20/40 BSCVA, graft thin and clear. On loteprednol (Lotemax) qd
because of steroid response, AST qid.
 12/10/2009 - BSCVA 20/30- on loteprednol and AST bid.
 3/4/2010 - VA drops to 20/70 because patient forgets to use AST. 1+ central
PEK in the graft. Restarted AST q2h and will see again in 4/2010.
Case Detail - Patient #10
 1/27/2009 - 64 YO male with long hx of HZV keratitis with neurotrophic cornea
complicated with bipolaris fungal infection OS.
 3/9/2009 - Perforation despite signs of resolving infection, glued.
 4/13/2009 - Glue gone and flat AC. VA light perception with projection.
 4/15/2009 - PK OS - Postoperative voriconazole (signs of fungal elements in recipient
button), PF dexamethasone (PF dex) q2h.
 4/29/2009 - Stopped voriconazole and started AST q2h, also on brimonidine/timolol
(Combigan) and travaprost (Travatan Z) for elevated IOP secondary to extensive
peripheral anterior synechiae (PAS).
 6/30/2009 - Stopped PF dex for difluprednate (Durezol) tid. Planning for phaco with
IOL for dense cataract. AST qid. VA no better than HM despite clear graft.
 7/31/2009 - Confluent PEK inferior one third of graft. Restarted PF dex qid and D/C
difluprednate. Increased AST to q2h. Azithromycin (Azasite) to lid margins qd.
 8/30/2009 - Phaco with IOL OS. PF dex and AST q2h after surgery.
 9/30/2009 - UCVA - 20/40, BSCVA - 20/40. Now on prednisolone acetate 1% (Pred
Forte) instead of PF dex. Graft thin and clear.
 3/1/2010 - Same vision, graft thin and clear. Meds: AST q3h, loteprednol bid,
travaprost qd, brimonidine/timolol bid.
 Photos Preop on Next Slide.
Preop Photo - Patient #10
Discussion - The Problem
 The general consensus is that PK in neurotrophic corneas is very high risk to the
degree that many recommend no surgery unless complications dictate (perforation or
near perforation) or in the case of poor vision in the fellow eye.
 Previous studies have shown comparable results in HZO patients but required lateral
tarsorrhaphy in many of those eyes for success. Reed and colleagues reported on
12 (10/12 grafts clear and 9/12 with vision better than 20/80, average 3 year followup), and Tanure and associates reviewed 15 (13/15 clear and 8/15 with VA better
than 20/100, average follow-up 50 months).
 The results here are comparable or better than those reported, without the use of
lateral tarsorrhaphy.
 Although average follow-up is shorter, 80% of grafts were clear and 90% of
epithelium clear and 100% intact. 70% were 20/40 or better and 90% 20/80 or better.
None of the 3 patients with vision worse than 20/40 had that attributable to corneal
opacity or irregularity.
 AST appears to be a valuable, if not essential adjunct to PK in these high risk eyes
Discussion - The Answer?
 Alternatives to AST include epithelial growth factor, nerve growth factor, allogeneic
serum, autologous platelet-rich plasma, umbilical cord serum and substance-p
derived peptide with insulin-like growth factor 1.
 None of these have the accessibility of AST for the average patient.
 Despite the instability of some of the growth factors present in serum, the preparation
can be frozen and maintain clinical efficacy of up to 4 months and refrigerated up to 4
days.
 AST has been used for healing epithelium in a variety of settings where is has ceased
to grow.
 In surgical situations it has been used following vitrectomy in diabetics and post
lamellar corneal surgeries.
 Only one case was reported of AST use following PK by Fernando and colleagues in
the setting of graft-versus-host disease.
 In this series once the initial 2 cases had shown stability following keratoplasty (both
had required AMT to heal non-healing defects pre-PK), the decision to offer treatment
to other patient became easier.
Discussion - Recommendations
 Use of autologous serum tears (20%, AST) and preservative-free
dexamethasone is an effective strategy to avoid epithelial complications
following PK in the setting of neurotrophic keratitis, HSV, HZV and mild
limbal stem cell deficiency.
 If the results of this series are borne out over a longer term, this approach
could change basic recommendations about keratoplasty in these high risk
eyes.
 The success in one patient with multiple graft failures from recurrent HSV
and rejection (the former preventing aggressive treatment of the latter)
suggest exciting possibilities for the management of PK’s in the setting of
HSV.
 Despite the limitations of the study (historical, no preoperative quantification
of corneal sensation, relatively short follow-up, selected patient enrollment),
the results argue the value of an expanded study of the role of AST in the
management of keratoplasty in general and particularly in high risk cases.
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