Cornea: Notes

Corneal Notes
Dr Yong Meng Hsien
Lecturer & Ophthalmologist, UKM & HCTM
yongmenghsien@ppukm.ukm.edu.my
Last edited: Feb 2022

Keratitis
• Hx: symptoms (pain/red/BOV/discharge), risk (ocular/systemic)
• PE: lesion (size/level/visual axis/location),
– pseudomonas: ground glass, wet sloughy, rapid
– fungal: endothelial plaque, satellite, fluffy
– acanthamoeba: epitheliopathy, ring abscess, perineuritis, pain > lesion,
limbitis/LSCD
• Ix: corneal scraping for stain/C&S (50% +ve)
• Ix new: confocal microscopy (esp fungal/Acantamoeba), PCR, AS OCT
• Rx:
– Bacteria: mono (fluoroquinolone/cipro 0.3%/moxi 0.5%) or dual
(cephalosporin- cefuroxime 5% & aminoglycoside- gentamicin 0.9%)
– CL-bacteria (gram -ve/psuedo): mono (> ciloxan 0.3%) or dual
(ceftazidime/fortum 5% & genta 0.9%)
– CL-acantamoeba: dual with atleast 1 biguanide (Chlorhexidine
0.02%/PHMB 0.02% + diamidine/propamidine 0.1%/hexamidine) + epiT
debride (atleast 6-12mth)
– Fungal: mono (natamycin) or dual (ampho B 0.15%/fluconazole
0.2%/oral) + epiT debride (atleast 2-3-mth)
– non response: stop AB re C&S, if >2wk KIV transplant
– systemic if: sclera/limbal, perforation, endophthalmitis
– steroid: SCUT/for high inflam/sclerokeratitis/scarring
– surgical keratoplasty

Common Ab @ Cornea
• Cephalosporin
– Cefuroxime, cefazolin
• Aminoglycoside
– Gentamicin, tobramycin
• Tetracycline
– Doxy-,
• Macrolide
– Azithro- mycin
• Quinolone
– Cipro, Moxi, Levo

DDX- infectious keratitis
• CL related: pseudomonas, acanthamoeba,
fungal
• IK
– syphilis (congenital @ 5-25yo > acquired)!
• acute: granulomatous AU, limbitis/salmon patch, deep
stromal V
• chronic: stromal feathery scar, ghost vessel
– HSV/HZV, TB, Lyme, parasite
– DDX inflam: Cogan (autoimmune vasculitis w ear
s/o, >peripheral cornea), sarcoidosis

Causes: CU & CM
Corneal Ulcer
• Infectious
– bacterial/viral/
protozoan/fungal
• Non infectious
– Sterile
– Shield
– Neurotrophic
– Immune-related
– trauma/chemical/thermal
– Nutritional (Vit A)
• Mixed
– interstitial, hypersensitivity,
exposure
Corneal Melting
• ifx & inflam (like CU)
• others
– dry eyes
– ectasia (congenital/degen)
– iatrogenic (MMC/LASIK)
– trauma

CU: Hx/PE
• Onset: gram –ve > +ve > fungal
• Risk: ocular & systemic
• Acanthamoeba: CL + H20 + high pain, early
epitheliopathy (ridge/dendrite-like), ring
infiltrate, radial perineuritis, high immuno
response, limbitis/LSCD
• Pseudomonas: CL + ground glass, aggressive,
Wessely ring
• Fungal: slow, feathery/fluffy, satellite,
endothelial plaque, worsened by steroid!
• Viral: epiT/stromal/endoT → reduce
sensation, uveitis, recurrence

CU: Specific Signs
Ring Infiltrate
• Pseudomonas
• Herpes
• Fungal
• Acanthamoeba
Wessely ring
 pseudomonas
 HSV/HZV
Intact EpiT
• LHDN
Evidence of healing
• symptoms
(pain/discharge/VA)
• infiltrate (density)
• corneal edema
• AC cell/hypopyon
• Ocular surface/tear

Rx- Principles
• Control infection (sterilization phase)
• Corneal scraping/stain/C&S +- PCR
• Antimicrobial (topical +- systemic)
• Sterilization phase (48-72H) VS healing phase
• Control inflammation (healing phase)
• steroid
• Promote re epithelialization (healing phase)
• Doxycycline, Vit A, topical AT/NAC/terramycin
• Symptoms relief
• Cycloplegic/pain killer
• Common pitfall
• delay in Dx, inappropriate sample collection, inadequate therapy, drug
toxicity, and delayed follow- up

Corneal Scraping- Details
• before AB/12H stop AB
• Perservative free LA/b4 fluorescein
• No 15 blade/25G needle/Kimura spatula
• Edge (area of uninvolved to involved)
• Avoid thin area
• Gram stain/KOH/C&S (blood/chocolate/Mc
Conkey/Sabouraud)
• Extra:
– conj swab
– epithelium for virology C&S/PCR
– non nutrient agar with E.Coli for Acanthamoeba (CL case), transport
with page’s saline
– Propionibacterium need 2wk C&S
– confocal microscope for hyphae/acanthamoeba cyst
– AC tap
– corneal biopsy (2-3mm trephine/base & edge) for HPE & C&S
– Giemsa stain instant result and equal sensitivity for fungal (vs Gram)

Antimicrobial
• Bacteria
– Dual: ceftazidime 5%/cefuroxime 5% + gentamicin 0.9% or quinolone
– Mono: quinolone
• 2nd gen (cipro-/o-floxacin): less spectrum
• 3rd/4th gen (levo/ganti/moxi-floxacin): less pseudomonas activity
• Fungal (3/12 Rx/NO steroid! +- epiT debridement))
– Dual: amphotericin B 0.15-0.5% + fluconazole 0.2% or oral 200mg BD
– Mono: natamycin 5% (>filamentous/fusarium), voriconazole 1% (both)
• Viral (+- prophylaxis)
– aciclovir occ, oral 400mg 5x (HSV) or 800mg 5x (HZV), or famcidar
– need epiT debridement (penetration)
• Acathamoeba (1-2H x 2wk  taper QID x 6/12 Rx)
– Biguanide (for cyst/trophozoite)- PHMB or chlorhexidine 0.02%
– Diamidine- Propamidine/Brolene 0.1% or hexamidine
– need epithelial debridement (remove nidus + penetration)
– CXL (riboflavin x 30min UV)

Acanthamoeba
• First-line therapy is biguanides, chlorhexidine gluconate 0.02% to 0.2%,
or polyhexamethylene biguanide (PHMB) 0.02% to 0.06%, with
monotherapy a consideration for early cases. Δ
• For chronic or later stages, dual therapy with propamidine isetionate
0.1% (Brolene, Sanofi-Aventis), or oral or topical voriconazole 1% may be
needed to reduce resistance to therapy. Δ
• Dosing is hourly for a continuous 48 hours, followed by hourly while
awake for the next 72 hours, then q2h to q3h for 3 to 4 weeks. Dosing for
the oral anti-fungal agent is 200 mg twice a day. Response to therapy may
not be apparent for up to 2 weeks.
• For refractory cases lasting 3 to 4 months, miltefosine (Impavido,
Profounda, Inc.) is an FDA-approved oral medication for Acanthamoeba
keratitis dosed at 50 mg t.i.d. and continued until resolution of the
keratitis.
• Early amoebic keratitis is mainly intraepithelial, and debridement
reduces the microbial burden while facilitating antibiotic penetration

ACSIKS 2018
• 6626 eyes (>male in general + w trauma, >female w CL)
• Bacterial38% vs fungal 33% vs viral 13%
• Major risk (trauma 35% > CL 11% > prior ocular surgery
7% > ocular surface dz 4%))
• Fusarium 18% > Pseudomonas aeruginosa 11% >
Aspergillus flavus 8% > Strep pneumoniae 6%
• Cornea transplantation 46% failed
• Moderate visual impairment (<20/60) 54%
• ACSIKS Clinical Protocol
• ACSIKS Microbiological Protocol
• Study did not standardize the treatment

Mycotic Ulcer Treatment Trial (MUTT)
There are two MUTT:-
MUTT I (2013): for filamentous fungal ulcer especially Fusarium species,
topical natamycin 5% was associated with significantly better outcomes
compared to topical voriconazole 1%.
MUTT II (2016): for filamentous fungal ulcer that being treated with topical
natamycin 5% and topical voriconazole 1%, the addition of oral voriconazole
does not appear to be beneficial.
smear-positive ulcers presenting in eyes that have vision between 20/40 and
20/400, topical natamycin 5% (Natacyn, Alcon) was found effective. For more
severe mycotic ulcers presenting with 20/400 visual acuity or worse, the
management of topical natamycin 5% (Natacyn, Alcon) was combined with
voriconazole 1%.

Antibiotic Precipitates
• Ciprofloxacin @pH of 4.5
• Moxifloxacin @pH of 6.8
• Normal ocular surface pH @7.5, but can
increase during infection.
• As the pH rises, antibiotics can become less
soluble and precipitate onto the cornea
• Moxifloxacin is more soluble than
ciprofloxacin at tear-film pH and is thus less
likely to form corneal precipitates.

Antifungal
• topical natamycin 5% is limited by its poor penetration into the
corneal stroma
• Topical amphotericin B 0.3% to 0.5% is an alternative, but its use
requires access to a compounding pharmacy and is limited by
toxicity.
• Voriconazole, a newer-generation triazole, has gained popularity
in the treatment of fungal keratitis because of its excellent ocular
penetration
• intracameral injection of amphotericin with or without hypopyon
drainage
• intrastromal injection of voriconazole
• at this time, topical natamycin remains the most evidence-based
treatment for filamentous fungal keratitis, and adjuvant oral
voriconazole should be considered if the organism is Fusarium

Intrastromal Injection
• Peribulbar, sterile/OT/microscope
• Needle bevel down, inserted obliquely from the
uninvolved clear area to just reach the abscess at
mid-stromal level
• Inject till amount of hydration of the cornea is
used as a guide to assess the area covered, then
plunger is withdrawn slightly to ensure
discontinuation of the capillary column and thus
prevent back-leakage
• At least 2 (2-5) deposit surrounding the lesion
(circumferential/barricade)

CU: Supportive Rx
Doxycycline/tetracycline
• Antibiotic: esp for
blephalitis/meibomianitis (lid flora)
• Collagenease (matirx
metalloproteinase) inhibitor →
reduce breakdown/melting of
corneal tissue
• Altering meibomian gland function
to lower free fatty acid production
• Systemic Ab (Cipro 750mg BD): if
+endopth, limbal involved,
impending perforation
• Vit C: corneal thin/melt
Steroid
• controversial/SCUT showed no
difference
• never used alone/b4 antimicrobial +
low dose if ED + monitor melt
• Pros: reduce inflam/scar, for ED
• Cons: promote ifx, reduce collagen
synthesis
Admission: severe ifx, non-compliance
Tectonic graft: perforation/failed glue,
at least 2d intensive Rx
Therapeutic graft: non response,
large, infiltrate near limbus esp fungal,
melting

Corneal matrix metalloproteinases (MMPs)
• MMPs are a family of Zn2+-dependent enzymes responsible for
degradation of the components of the extracellular matrix
(including proteoglycans and various types of collagens) during
normal development as well as in disease processes.
• only MMP-2 proenzyme has been found in the normal healthy
cornea.
• However, after corneal injury, additional MMPs (including MMP-
1, MMP-3, and MMP-9) are synthesized.
• The proteinase inhibitors of the cornea play a key role in corneal
protection by restricting damage during corneal inflammation,
ulceration, and wound healing.
• Many of these inhibitors are synthesized by resident cells of the
cornea; some are derived from tears, aqueous humor, and limbal
blood vessels.

Steroid for infectious keratitis
• benefit of limiting corneal melt and
neovascularization versus the risk of potentiating
the infection and further complications from
delayed epithelial healing
• clinically significant benefit in visual outcomes
using steroids when: 1) used early, 2 to 3 days,
after antibiotic pretreatment; 2) severe ulcers
presented with acuity of counting fingers
regardless of depth of involvement or thinning;
and 3) there were invasive rather than cytotoxic
strains of P. aeruginosa. Δ Δ

Keratitis: Key studies & result
• Steroids for Corneal Ulcers Trial found that although steroids provided
no significant improvement overall, they did seem beneficial for ulcers
that were central, deep or large, non-Nocardia, or classically invasive
Pseudomonas aeruginosa; for patients with low baseline vision; and when
started early after the initiation of antibiotics.
• Mycotic Ulcer Treatment Trial (MUTT) I showed a benefit of topical
natamycin over topical voriconazole for fungal ulcers, particularly among
those caused by Fusarium.
• MUTT II showed that oral voriconazole did not improve outcomes
overall, although there may have been some effect among Fusarium
ulcers. Given an increase in nonserious adverse events, the authors
concluded that they could not recommend oral voriconazole.
• The Herpetic Eye Disease Study (HEDS) I showed a significant benefit of
topical corticosteroids and oral acyclovir for stromal keratitis.
• HEDS II showed that oral acyclovir decreased the recurrence of any
type of herpes simplex virus keratitis by approximately half
• New: ZEDS

SCUT
• 500 pt/multicenter-region
• topical prednisolone sodium phosphate
1.0% or topical placebo starting after a 48-
hour course of topical moxifloxacin 0.5%
• culture-positive bacterial ulcers
• overall data showing no difference in
outcomes such as 3-month visual acuity, 3-
month scar size, or rate of perforation

SCUT
• subgroup analyses suggested that corticosteroids are beneficial in certain
subgroups. Patients with low vision (counting fingers or worse) at baseline had 1.7
lines better vision at 3 months in the corticosteroid group compared with the
placebo group (P ¼ 0.03). Central ulcers, covering the central 4-mm pupil, that
were treated with corticosteroids also had better 3-month best spectacle-
corrected visual acuity (BSCVA) compared with placebo (w2 lines better; P ¼ 0.02).
Likewise, patients with deep ulcers at baseline fared better with topical steroids
(1.5 lines better; P ¼ 0.07). Timing of steroid administration also proved to be a
significant factor, with patients randomized to corticosteroids after only 2 to 3
days of antibiotics having better BSCVA at 3 months than those randomized to
placebo (w 1 line better BSCVA; P ¼ 0.01).
• Nocardia ulcers randomized to corticosteroids had 0.40 mm larger infiltrate or
scar size at 3 months compared with placebo (P ¼ 0.03), although this did not
result in worse 3-month BSCVA (P ¼ 0.21) (Fig 2).63 This trend continued at 12
months, with nonNocardia ulcers faring better with corticosteroids (1 line
improvement of BSCVA; P ¼ 0.02) and Nocardia ulcers faring worse (average scar
size increased by 0.47 mm; P ¼ 0.02; no difference in BSCVA).64 Overall,
Pseudomonas aeruginosa ulcers did not benefit from the addition of
corticosteroids; however, the classically invasive subtype of P. aeruginosa
demonstrated 2.5 lines of visual acuity improvement at 3-month BSCVA when
randomized to steroids versus placebo

CU: Mx of complication
Perforation
• Therapeutic CL/BCL
• Adhesive
glue/cyanoacrylate
• Amniotic membrane
(with suture/fibrin
sealant)
• Keratoplasty

Therapeutic PK @Infectious Keratitis
• Host trephine: 0.25-0.5mm > infective area
– +- retract/peritomy to see scleral involvement
• Donor trephine: as usual 0.25-0.5mm > recipient
• Cornea button: C&S, HPE, +-mycology
• AC wash out: antibiotic, antifungal
– Voriconazole 500ug/1ml (IC 50ug/0.1ml)
– AmphoB 50-100ug/1ml (IC 5-10ug/0.1ml)
• Subconjunctival: antibiotic, antifungal
– Genta + Fluconazole 2mg/ml
• Post op
– topical antibiotic + antifungal
– +- Subconj antifungal OD 3-7days
– Weak anti-inflammatory: NSAIDs/Nevanac +- systemic NSAIDs
– 2wk gap to consider topical CSA 0.5-1% BD  QID  FML BD  QID

Corneal Melt @immunosuppressed
• subtle features
• DDX ifx VS immune mediated VS dry eye
– clues >immune: systemic symptoms, a/e scleritis,
FBC lymphocyte count >1.2
– clues >ifx: infiltrate, lymphocyte <0.8
• Principle
– need scraping/C&S for all cases (subtle features)
– treat with Ab for all cases, adjust
immunosuppressant if necessary
– treat dry eye aggressively

Interstitial K
• Def: stromal inflam (predominant stroma OR without primary
endo/epiT inflam)
• Patho: immune mediated reaction
• Causes:
– Ifx: TB/syphilis/leprosy/herpes/onchocerciasis/Lyme
– Non-ifx: Cogan (a/w PAN/deaf), sarcoidosis
• SSX:
– Mid stromal opacity (late): feathery scarring with ghost vessels
– Mild stromal inflam (acute): limbitis, stromal vascularization/ bleed,
salmon patch, AU
– TRO granulomatous ifx (AU/KPs)
– TRO congenital syphilis (BL, onset 5-25yo, AR pupil & salt pepper
fundus)
– TRO Cogan dystrophy (BL, young, autoimmune vasculitis with
deaf/tinnitus/vertigo/CTD/retinal vasculitis)
• Mx:
– Screening for CTD/ifx
– Topical steroid +- AB (underlying ifx)

Endothelitis
• Inflam vs Ifx (or mixed)
• Ifx >virus (CMV/HSV/HZV/mumps)
• DDX: Posner-Schlossman, FHI
• CMV
– >Immunocompetent, not responded to aciclovir
– coin-shaped KPs (in cluster) +- edema/high IOP/AU
– 4 forms (based on edema + KPs)- linear, sectoral, disciform,
diffuse
• Ix: Aq PCR, Goldmann-Witmer coefficient >3 (local
production of CMV antibody)
• Mx: topical ganC + systemic valGan (BD 6/52 then OD
6/52 at least) & topical steroid

Non-infectious Keratitis
• Recurrent erosion syndrome
• Filamentary keratitis
• Thygeson’s SPK
• NK

Keratoplasty
• Indications x 4: TTOC
• Types & Main indications:
–PK (>KC/PBK/CD)
–Ant lamellar
•DALK (>KC/CD/keratitis)
•PTK (>ant 50-75um)
•SALK (>ant ⅓)
–Post lamellar (>FED/PBK)
•DSEK/DSAEK
•DMEK
–Keratoprosthesis (if multiple graft failure/surface
dz)

Question of Corneal Transplant
Short notes
1) Indications of corneal grafting
2) Storage of donor tissue
3) Prognostic factors of PK
4) Post-operative complications of PK
5) Graft Rejection VS failure
6) Paediatric corneal transplant
7) Lamellar keratoplasty
8) Keratoprothesis
Long Question
1) Donor selection
2) Causes of graft failure , clinical feature, Mx & immunological basis of
transplant rejection?
3) Indication of grafting and prognostic factor

Storage of Corneal Graft
1. Short term (days)
• Moist chamber (humidity 100%/4°C/for 48H)
• McCarey-Kaufman medium (standard tissue culture medium-
TC199/D5%/Ab/4°C/for 2–4D)
2. Intermediate term (weeks)
• Dexsol/Optisol GS/Ksol/Procell
– standard tissue culture medium- TC 199
– chondroitin sulphate 2.5%
– HCO3 buffer/amino acid/Vit C & B12/D1%/gentamicin
– 4°C/for 2 weeks
• Organ culture (low rejection but high infection rate/37°C/for 4 weeks)
– >complex >cost >opaque cornea on op, but can keep longer)
3. Long term (months)
• Cryopreservation (liquid nitrogen/-196°C/for 1 year/expensive and unpredictable
results; usually not suitable for optical grafts)

Keratoplasty: Prognostic Factors
The big 4
• Ocular inflammation
• Glaucoma
• Corneal vascularization
• Ocular surface abnormalities (lid/tear/neurotrophic)
Others
• Underlying eye disease
– (Brightbill’s classification I → V, KC/CD > FED/PBK > keratitis >
glaucoma/paeds cases > SJS/OCP/chemical/burn)
• AC problem (PAS/rubeosis/cataract)
• Post segment (retinal/CMO/Optic atrophy)
• Visual potential (amblyopia)
Management
• Preop assessment (Visual potential, IOP/AC cell/dry eye/blepharitis)
• Preop topical antibiotics / steroids / cyclosporin A if necessary

Brightbill’s Classification:
Corneal Graft Prognosis
• Grade I to V (excellent to poor)
• Underlying pathology + secondary complication

Donor graft assessment
Systemic diseases
• extreme age: < 2yo ( difficult to handle/to small/friable/steep K 50D), >
65 years
• death to preservation time <12-18H
• Death/CNS dz from unknown cause
• Infections (rubella, rabies, hepatitis, AIDS, syphilis,
encephalitis/septicemia/IE)
• Malignancies (leukemias, lymphomas, disseminated cancer)
• severe hemodilution: Affects accuracy of serological testing
Ocular factors
• +- Intraocular surgery
• glaucoma/uveitis/tumors
• low endothelial cell count <2K
• +- prev refractive surgery

• Lions Eye Donation Service,
• Melbourne, Australia. The standards and guidelines of the
• Eye Bank Association of Australia and New Zealand[2] and
• the Therapeutic Goods Administration of Australia[3,4] were
• employed and followed. Donor history was obtained from
• hospital medical records and from medical records of the
• donor family physician. Further history was obtained from
• a knowledgeable historian during a donor risk assessment
• interview, which included explicit questions regarding
• previous ocular surgery, pathology, refractive procedures,
• or therapies. All corneoscleral discs underwent routine
• screening, which included in situ penlight examination, slit
• lamp biomicroscopy examination of the excised corneoscleral
• disc, specular microscopy of the endothelium, placement into
• organ culture preservation media with repeat microbiological
• testing, and light microscopy examination at the end of the
• storage period. Reported demographic and clinical data were
• taken from clinic and eye bank medical records.

• may not be able to detect pathologies such
• corneal scars or previous corneal laser
refractive surgery scars.
• previous laser-assisted in situ
keratomileusis (LASIK) surgery
• o incorporate AS-OCT imaging of donor
corneal tissue into
• routine eye bank screening procedures

PK- Procedure
• Recipient size: 7.5-8.0mm
• If more +reject/PAS/glaucoma, if less high astig
• Donor size: 0.25-0.5mm larger
• >watertight/AC depth/flattening (less astig), <PAS/glaucoma/wound gap
• Prepare cornea surface
• mark center +- radial keratotomy marker (suture placement)
• Flieringa scleral fixation ring with silk 7/0 (esp pseudo/aphakia/post tppv/low sclera rigidity)
• Prepare AC
• paracentesis and fill AC with OVD
• Donor button
• cut from endothelial side using a trephine (hand-held, gravity, vacuum-driven- Barron).
• Host button
• trephine (Katena/blade) stopped at the DM/first release of aqueous  slower decompression
with the blade or corneal scissors.
• Suture
• cardinal sutures: use 4 to 8 10–0 nylon
• Complete suturing: interrupted sutures (often 16 in total) or a continuous running suture
• Key: 90% depth, watertight with mild eversion, buried
• Adjust suture tension to minimize astigmatism (handheld karatometer)
• Refill AC with BSS/sunconj dexa&genta/pad with occ maxitrol/+-BCL
• Post op: topical steroid/Ab/mydriatic, +- systemic steroid/aciclovir (HSV)/diamox (avoid
topical antiglaucoma
• TCA & cornea topo/ref  STO PK 12mth (adjust continuous suture aft 1/12), DALK
6/12, stat if loose

PK + cataract extraction
• better intraoperative visibility
• prompt visual rehabilitation
• avoids later cataract extraction and graft endothelial loss.
• inability to accurately estimate IOL power (unpredictable postoperative
keratometry and suture-induced astigmatism)
• Cataract extraction- open-sky when view is poor
• Closed-chamber phaco followed by a penetrating keratoplasty (if good
view):
– decrease open sky time
– allow a rhexis and in-the-bag IOL placement.
– Phaco incisions should be scleral or limbal and short
• For active corneal ulcers, if performing a therapeutic keratoplasty, the
crystalline lens should be retained as a barrier to pathogen entry into the
posterior segment

EK- DSEK/DSAEK/DMEK
• 3-6mm limbal/scleral incision (varies)
• DM stripping: descemetorrhexis (reverse Sinski hook) + air in AC/vision blue
(increase contrast)/OVD/BSS irrigation
• Graft insert: glide/Busin/push-through (centration/gentle)
• Adhesion: air bubble full x 10min
– +- venting incision, peripheral bed scrapping, roller sweeping
– Optional PI (inferior)
• Post op: gutt steroid/AB/position  IOP/air/graft check
• Cx intraop: donor/host cornea injury/centration
• Early post op: graft decenter/double AC/detach vs pupillary block
• Late post op: epiT ingrowth, interface problem, Ref change, cataract, graft
failure/rejection, endoC loss 50% in 5yr
• Air bubble pupillary block- prevention:
– Dilate pupil
– Lying position
– Inf PI
• DMEK- better VA outcome/less rejection, more difficult
• New theories: endoT migration, endoT transplant (DMET)

• pre-Descemet’s EK (PDEK), utilising three techniques that
I have described to increase success and repeatability –
endoilluminator-assisted PDEK, air pump-assisted PDEK and
host Descemetic scaffolding.
• remove a non-cataractous crystalline lens too as the risk
of cataract developing secondary to air tamponade,
prolonged steroid usage, inflammation, natural ageing etc.
is high and can result in the need for surgery, which can in
turn cause loss of precious graft endothelial cells
• air pump-assisted PDEK technique allows synechiolysis
under air tamponade and prevents bleeding from the iris,
hyphema and a fibrinous atmosphere. It helps achieve
effective intraoperative graft attachment

• DSAEKStd- 150um
• thin- 135um
• ultrathin- 100um
• nanothin-50um
• DMEK- 25um
• PDEK-35um
• thinner faster visual rehab/recovery, less
rejection
• thinner more challenging in handling, >detach
esp in higher risk (ACIOL, aphakia, post PPV)

DALK
• Ant lamellar down to DM
• IndiC: stromal dz w normal endoT
– Esp corneal ectasia, stromal scar, corneal ulcer/impending perforation
– Less rejection/astig, stronger wound, non penetrating, less donor criteria
– +interface opacity
• Partial corneal trephine till target level, depth around 90%
– Trephine complete turn 250um, quarter 62.5um
• Melles with manual lamellar dissection
– Stepwise: remove 70% ant lamellar with crescent blade/Devers dissector
– Paracentesis and separate stroma-DM: w Healon or cyclodialysis spatula
– Remove/resect with curved corneal scissor
• Big bubble Anwar technique (pneumodissection)
– 27/30G needle or Fogla dissector w 25G cannula
• +- air bubble in AC- to confirm DM detachement
• Oversize graft 0.25mm only
• Convert to PK if DM rupture
• Early STO 4-6mth
• Dia-DALK techniques

DMEK/DSO
● relatively small area of abnormal Descemet membrane
and endothelium
● (descemetorhexis) resulted in mitosis of normal
endothelial cells from the periphery, leading to
● resolution of the edema and improvement in vision. In
the future, more traditional keratoplasty
● may be replaced with descemetorhexis combined with
topical and/or intracameral Rho kinase
● (ROCK) inhibitor to stimulate endothelial proliferation.
Another future treatment may be
● injection of the patient’s own cultured endothelial cells.

Post PK- Cx
• Intraop
– Trephine/handling of host/donor related
– Open sky related/intraocular content injury
• Post op (TRO ifx/inflam-rejection/failure without rejection)
– Primary/early failure <72H>
• Cornea graft (PED >2wk/leak/rupture/ifx/endoph)
• Suture (loose/tight/ifx/jetting)
• AS (flat/glaucoma/uveitis)
• Fixed dilated pupil @ Urrets-Zavalia)
– Secondary/late failure
• Graft rejection (>2wk)
– causes: HLA/ABO (collaborative corneal transplant study- >ABO), sensitization of
recipient by donor cell (afferent arm), immune reaction/rejection (efferent arm)
– SSx: circumcorneal injection, epiT (line/elevation/Krachmer), stroma (haze), endoT
(KPs/Khodadoust line), uveitis
– Mx: early aggressive topical/systemic steroid
• Suture (astig/break), wound (epiT ingrowth/membrane),
glaucoma/uveitis/CMO/recur dz

Post op steroid
• PK: Topical prednisolone acetate 1% or dexamethasone
sodium phosphate 0.1% every 2, 3, or 4 h initially is then
slowly reduced over a period of 6–12 months but
maintained once daily indefinitely
• Immediate postoperative subconjunctival injections of
methylprednisolone acetate 40 mg/mL or dexamethasone
disodium phosphate 0.1%
• if the eye is not phakic or experiencing steroid-
responsive glaucoma, once-daily steroid drops should be
continued indefinitely after DSAEK
• DMEK weak topical steroid once daily indefinitely,
especially in pseudophakic and controlled patients with IOP
• maintain DALK patients on topical corticosteroids at least
once daily for the first 12 postoperative months.

Corneal Graft Rejection RX
• Systemic:
– Oral Pred 1mg/kg (max 80mg) 1-2wk then taper
• Paeds:
– IVMP 500mg-1g, 1-3days
• Paeds: IVMP 10-30mg/kg/day x 3-5d (max 250mg tds or 10mg/kg tds)
– CSA
• Local:
– Subconjunctival: betamethasone 2-3mg , dexamethasone
phosphate 2-4mg, 0.5-1.0ml
– Topical (a must): maxidex/pred forte as frequent as hourly &
RTC/maxitrol ointment ON  taper slow
• Need >4wk for Rx response/considered failed
• Others:
– collagen shield soaked in corticosteroids

• topical prednisolone acetate 1% every hour
and systemic oral prednisone 1 mg/kg usually
tapered over 6–8 weeks
• subconjunctival betamethasone 2 mg
injection and dexamethasone 0.1% drops in
the affected eye every hour for 24 h.
• subconjunctival injection of triamcinolone
acetonide 20 mg, in combination with the
topical application of prednisolone acetate
1%,

Post PK high astig- Mx
• Usually -4 to -5
• Suture removal-glasses-CL
• Relaxing incision/compression suture/coupling
• IOL exchange/piggyback/toric IOL
• PRK/LASIK
– At least 1yr post PK, 4/12 post all STO, if continuous
suture adjust aft 1/12
• Maloney intraoperative keratometer
• postoperative suture adjustment: selective
suture removal or suture replacement

Keratoprosthesis
• =artificial corneal implant
• IndiC:
– Unsuitable for keratoplasty
– Severe LSCD (SJS/chemical)
– Multiple failed PK/AMT/LSC Tx
– BL poor vision (normal ON/retina Fx)
• Types:
– OOKP- osteo-odonto-Kpro (tooth root/alveolar bone + center
optical cylinder, 2 stages 2-4mth apart)
– Boston Kpro (aphakic or pseudophakic)
– LVP KPro
• Pre op assessment
• Cx:
– Corneal/Kpro- retroprothesis membrane, cylinder tilt/extrusion
– Others: glaucoma (difficult monitor), RD, endoph

Temporary KPro TKP
• Landers 3rd-gen wide-field TKP-
– PMMA
– 1mm cylinder protruding to the anterior chamber (diameters: 6.2/7.2/8.2
mm). New trunkless fix size up to 8.5mm corneal opening.
– mushroom-shape corneal surface: diameter 15.5mm
– 6 suture holes in the periphery- sutured to the limbus using Vicryl 6.0 or 8.0
• Corneal trephine size: 0.2mm less than TKP
• If combine PKP: donor corneal 0.25-0.5mm oversized
• Others: endoscopy-assisted PPV, open sky PPV, stage surg (PK then
PPV)

Bowman Layer Transplantation
• Indications: keratoconus, postrefractive scarring/persistent
subepithelial haze, Salzmann nodular degeneration
– reestablish the physiologic barrier between the epithelium and anterior
stroma
• Preparation: manual stripping and femtosecond laser ablation
– Manual: epithelium debrided  trypan blue dripped  cornea lightly
scored just inside limbus 360 w 30-gauge needle  nontoothed forceps to
grasp BL cut edge & peel from stroma  roll  thinner (11mm) w shaggy
stromal remnants
– Femtosecond: thicker (37mm) but displayed smooth-cut posterior surfaces
• Transplantation: inlay or onlay (sutureless)
– Inlay: mid stromal pocket (manual/femtosecond), insert via glide
– Onlay: epi debridement, BL on top with AMT/BCL

Number @ Corneal Transplant
• Graft survival rate: 95% at 5yr (low risk case)
• Graft failure rate: 35% at 3yr (high risk case)
• Mean keratoplasty to rejection time: 19.8 ±
20.4 mth (majority within 1 ½ year)
• Rejection to failure rate: 50%
• Rejection site: endoT 50%/mixed 40%/epiT
2%/subepiT 1%
• EndoT cell loss post op: 60% at 3yr

Corneal Immuno-privilege
• 6 points
• 3 absent/low (afferent blockage)
– No vessels
– No lymphatic system
– Low expression of MHC Ag
• 3 present/high (efferent blockage)
– ACAID/immune-tolerance
– FAS-ligand/TNF/CRP (T cells apoptosis)
– Immunomodulator e.g. TGF-B, a-MSH (inhibit T
cells/complement)

Combine or stage surgery
• anterior chamber depth
• corneal surface  keratometer
• type of lens implant to use
• desired refractive outcome

• DMEK in pediatric patients, however, may
be more challenging attributable to difficulty
stripping the host endothelium, more
aggressive intraocular inflammation (including
a predisposition to generate fibrin) and
challenges with postoperative compliance

GDD in corneal transplant
• Cornea Glaucoma Implant Study Group
demonstrated that in patients requiring a
corneal transplant and a glaucoma tube
shunt, the incidence of graft failure and
immunologic rejection was decreased with
pars plana insertion of the tube

Corneal Transplant Registry
• European Cornea and Cell Transplantation
Registry (ECCTR)
• information on the recipient, donor and eye
bank processing
• transplant procedure and two year follow-up
including graft survival and failure
• patient-reported outcome measures (PROMs)
• addition of a limbal stem cell transplant
component to the registry

Keratoconus
• Def: progressive/triad:-
– Central/paracentral stromal thinning + Apical protrusion +
Irregular astigmatism
• Aetio (6C):
– Primary: idiopathic/AD w FHx (10%)
– Secondary (ocular): VKC/eye rubbing/CL/aniridia/blue
sclera/Leber/RP/floppy eyelid
– Secondary (systemic): Ehlers Danlos/Marfan/OI/Down
– Aggravated by refractive surgery
• Class:
– Mild/mod/severe: K 48-54 OR forme fruste/early/late OR
Amsler Krumeich stage I-IV
• Histology:
– epiT scar/iron, fragmentation of Bowman’s, thin stroma, DM
fold/break (only in hydrops)

Key Questions
• KC vs other ectatic diseases
• KC all about
• Corneal topography VS tomography
• Staging & Progression
• Management

Global Consensus on Keratoconus
and Ectatic Diseases 2015
• Currently, there is no consistent or clear
definition of ectasia progression
• Currently there is no clinically adequate
classification system for keratoconus and that
the historical Amsler–Krumeich classification
fails to address current information and
technological advances

Keratoconus- SSx/Ix
• SSX: onset puberty → BL/asym (50% within 16yr)- BOV with
unstable ref +- hydrops attack
– Inspect: Munson
– Torch: Rizzuti for cone (nipple/oval/globus)
– Direct: Oil droplet (Charleaux)
– Retinoscope: scissoring
– Placido disc
– Slit lamp: Vogt striae (vertical/stroma), prominent nerve, Fleischer
ring (iron @basal epiT, in blue)
+ stromal thin/cone protrusion/hydrop (DM rupture)/scar
(epiT/Bowman)
+ evidence of atopic eye dz + syndrome + CL/Rx related problem
– Keratometer/corneal topo: sym bow-tie → irreg astig (inf temporal
steep) + 2eyes mirror image/enantiomorphism
• Rabinovite-McDonell criteria: K >48/astig >1.5D/I-S asym >1.7D/CCT <450um @
thinnest/skewed radial axis >21degree/centra-thinnest cornea difference >20um
– Orbscan/pentacam – post corneal curvature (forme fruste)
• Berlin-ambrosio index
– Pachymeter- in case for CXL (450um)
– Ant seg OCT- scar level in case for PK/DALK

Belin ABCD KC Staging
• Ant & Back radius of
curvature (3mm),
• Corneal thickness
(minimal)
• Distance VA
(DCVA)

Pentacam for KC
• Topo + Ref + Astig + Km + CCT  AK classification
• K Max & ABCD & Thinnest pachy  progression
– Ant & Back radius of curvature (3mm), Corneal thickness
(minimal), Distance VA (BCVA)
• Indices  colour code, KISA (60-100), IS (1.4-1.9)
• BAD D (enhanced ectasia)  screening & colour code
(change/different: ant 5-7 & post 12-16 )
• Covis biomechanical: CBI & TBI
• Asphericity/Q value: normal -0.01 to -0.8
– Q-val <0/-ve/oblate = normal or KC or post hyperop LVC
– Q-val >0/+ve/prolate = post myopic LVC
– Q-val=0/sphere

Keratoconus- Mx
• Acute MX + Visual Rehab + Progression prevention
• Hydrops (heal with scar in 6-10wk)
– Hypertonic saline/cycloplegic/BCL +- topical steroid
– Intracameral gas (DM tear)
• Visual rehab (conservative)
– Glasses/CL (soft → rigid/hybrid/piggyback → sclera)
• Visual rehab (surgical)
– DALK/PK (if h/o hydrops)
• Indications: scar/hydrops, intolerance to CL, failed others with poor VA
• Principle: large graft slight eccentric (more than base of cone/Fleischer ring)
– Phakic IOL
– Intrastromal corneal ring segment (laser/manual)- for CL tolerance/VA
– Nodulectomy (central subepithelial scar)
• Progression prevention
– progress fast within 3yr, stable by 35yo (f/up + topo q3m  stable  6m)
– Progression= BCVA 1line or astig 0.75D in 18mth, or 12mth astig 1D/sphere -
0.5D/10um loss at thinnest part
– Treat atopic/VKC/avoid rubbing
– CXL (Dresden protocol or Averdo Accelerated CXL)
• Contraindicated in refractive surgery

Corneal Hydrops
• Prevalence 3%
• break in the Descemet’s layer  aq penetrate stroma  bullous
keratopathy
• Resolved spontaneously 2-6 mth
• Rx aims to reduce pain and reduce inflammation to prevent
further complications
• Topical cycloplegic, hypertonic saline and steroid & antibiotic
• intracameral air/gas injection or compression corneal sutures 
PK (60% need PK, higher risk of rejection)
• Longer duration > complications (infection, perforation, and
corneal neovascularization)
• +- improvement in UCVA due to drastic corneal flattening
following corneal healing or secondary scarring +- improve contact
lens fitting endpoints and even vision

CL for KC
• Mild KC- toric soft CL
• Mod KC- RGB
– Flat with apex contact- swelling/stain/scar risk
– 3-point touch- less apical contact, min peripheral touch
– Customisable e.g. Rose K/K2/K2 XL (for cornea with
graft)
• Combination lenses: piggyback RGB on soft base,
hybrid single piece
• Scleral CL: vault higher, more comfort, need saline to
insert
• Principle: repeat fitting for best fit,

CXL (or CCL/C3R)
• Intro: photochemical process for biomechanical stiffening & fibril stabilization
• Indications
– Progressive ectasia e.g keratoconus, PMD (to stabilize/slow progression/ +- reverse/reshape)
– microbial keratitis
– post surgery/LASIK ectasia
• MOA: photosensitizing agent/riboflavin + photochemical induction UVA (365-375um) +
O2  lysyl oxidase enzyme  free radical O2  covalent bond/polymerization of
collagen  strengthen bond 300%
• Procedure: CXL (Dresden protocol or Avedro Accelerated CXL)
1. CCT check (>400um) + recheck post epiT off + b4 UV/aft 30min riboflavin
2. Topical anest/clean (providone)
3. With or W/out epiT removal- alcohol loosening/crescent or beaver blade (8-9mm zone)
– Epi on: less effective (50%), but X pain X BCL, allow thinner cornea
4. Riboflavin/Vit B2
– Standard: 0.1% (in 20% dextran)- q2min for 30min b4 UVA + during UVA
– Epi-on: TE-CXL solution
– Thin cornea: hypotonic solution, add topical H2O,+- use of well (trephine/LASIK) to maintain hypo solution longer
5. UV-A light 370nm (270nm for keratitis): distance 5.5-6cm (guided by treatment area within
cornea)
6. Irradiance/power 3mW/cm2 (30min, total 5.45 J/cm2)- other option: 9mW (10min)
7. Rinse off with BSS  BCL  topical antibiotic/steroid

CXL
• Post op care:
– BCL for epi defect + topical AB (Cravit/Vigamox TDS/QID)- off aft ED healed
– Topical steroid: either post op or after epi defect healed- QID or lower (taper &
complete 1 mth)
– KIV pain relief (ED): cycloplegic, NSAIDs, pain killer
– Re-start CL after ED healed
– Wait at least 6/12 (up to 5yr) for stabilization for other surgery/CL fitting
• SE/Cx:
– Cytotoxic/keratocyte/limbus/endothelium (esp thin cornea) depopulation
– CXL haze- transient
– ED related Cx/ifx
– Corneal melting/scar
– X for pregnancy (+progression during pregnancy, to do b4 pregnant)
– X for RA/severe stromal scar
- Other (new):
- - CXL-plus: + PRK, + ICRS
- - LASIK-Xtra
- - Topography guided, variable fluence/pattern CXL
- - Maillard reaction in young DM (reducing sugar with natural CXL → no KC progression)

• The standard treatment protocol, called the Dresden
protocol[2], was formulated by Wollensak et al. for corneas
with minimal thickness of 400µm, and is as follows:
• Instill topical anesthetic drops in the eye
• Debride the central 7-9mm of corneal epithelium
• Instill 0.1% riboflavin 5-phosphate drops and 20%
dextran solution every 5 minutes for 30 minutes
• Exposure to UVA (370nm, 3mw/cm2) for 30 minutes
while continuing instilling the above drops every 5minutes.
• At the end of the procedure, apply topical antibiotics and
soft BCL with good oxygen permeability.

CXL
• epithelial-off standard (SCXL) VS accelerated
corneal collagen cross-linking (ACXL)
–Metanalysis IOVS 2018
–ACXL less decrease in: central corneal thickness
(CCT), and endothelial cell density (ECD),
–ACXL less reduction in: maximum keratometry
(Kmax)
–Same mean keratometry (mean K). VA

CXL: Standard Vs Accelerated Protocol
• ultraviolet-A (UVA) protocol of 3 mW/cm2
intensity at 370 nm over an exposure time of 30
minutes (now termed the ‘‘Dresden protocol’’).
• ACXL protocols are carried out in a shorter
period such as 3, 5, or 10 minutes by using 30,
18, or 9 mW/cm2 irradiance, respectively,
• with a cumulative irradiation dose of 5.4 J/cm2
• ACXL- potential advantages of reducing the rate
of complications such as corneal thinning, haze,
infection, and melting. However, it may affect
efficacy

Thin cornea for CXL
• Dresden protocol: minimal corneal thickness required is 400
µm.
• Modification: thickness 320-400µm  hypo-osmolar riboflavin
solution
– increase in thickness of up to about 25% of the original value
– Effective? Not compromised as the anterior stroma remains the same
while it is the posterior corneal stroma that swells + protect endothelium.
• Modification: higher concentration riboflavin of 0.2%
– increase the UV absorption in the anterior stroma and hence protect the
endothelium
• Modification: dextran-free riboflavin
– allow corneal thickness to increase
• Rescue: BSS saline onto well

CXL: Criteria & Progression
• Good candidates: mild to moderate disease
demonstrating Kmax > 47.0, inferior-to-
superior K ratio > 1.5, corneal thickness after
deepithelialization > 400 um, best corrected
visual acuity (BCVA) < 20/20, and evidence of
disease progression.
• Progression: no global consensus

Scleral CL
• Boston scleral CL
• Difficult fitting- need expert, expensive
• Ind: advanced KC

Early CXL for KC
• RGB mask progression

• Corneal Allogenic Intrastromal Ring Segments
(CAIRS). This utilises thin segments of de-
epithelialised and de-endothelialised donor
corneal stroma that is implanted into mid-
peripheral intra-stromal channels similar to
synthetic intra-stromal corneal ring segments
• flatten and regularise the cornea, centralise the
cone, decrease refractive error and improve
uncorrected and best-corrected visual acuity
while avoiding synthetic-related complications.

Keratoglobus
• Intro: Progressive/BL globular thinning/protrusion
(whole cornea)
• PathoP: collagen synthesis defect, non
inflam/hereditary (=KC/PMD)
• Primary (at birth) vs Acquired
– At birth DDX cong glaucoma, megalocornea/high
myope/deep AC/K 50-60D
– +-hydrops/rupture, no K ring/Vogt line
– a/w: Leber, blue sclera, Ehlers Danlos VI
• Rx: avoid trauma (rupture), same as KC

Peripheral Corneal Thinning
Quiet/Non inflammed/No ED/No pain
•Dellen
•Furrow degeneration
•Pellucid PMD
•Terrien’s TMD
Hot/Inflammed/+ED/+Pain (PUK)
•Infectious
•Non infectious
•PUK with autoimmune/systemic diseases (sarcoid/leukemia)
•Mooren’s
•Marginal keratitis

young 20-40s,
F=M, rare,
protrusion sup
to max
thinning,
+-scar/hydrops
/perforation

PUK
• Peripheral corneal stromal degradation.
• progress both centrally and circumferentially
• unresponsive to topical or conservative local
therapy
• collagenolytic and proteolytic enzymes
released from neutrophils and/or
macrophages

PUK- Rx
• liaise with renal physician/ rheumatologist if necessary
• Corticosteroids (pulsed IVMP 6-9 pulses or high- dose oral pred)
(NB >60y: bone density scans; calcium/ vitamin D supplements,
alendronic acid, gastric protection).
• 2nd line: methotrexate, ciclosporin, mycophenolate, azathioprine,
or continuous oral cyclophosphamide.
• Resistant cases = failed on two immunosuppressants, unable to
reduce oral steroid to <10mg daily  anti- TNF (adalimumab) or
anti- CD20 (rituximab)
• Topical: lubricant + antibiotic + steroid (caution thinning)
• Systemic: doxycycline, vitamin c
• Surgery: conjunctival recession, AMG, lamellar patch graft
• Other: CL, glue

Differences between
peripheral & central cornea
• Anatomic, physiology/immunologic
• proximity and contiguity with the sclera, episclera and conjunctiva
• Vascular: avascular central, peripheral- anterior conjunctival and deep episclera
vessels (0.5 mm into the clear cornea)  allow limited diffusion of Ig and
complement components into the cornea
• Lymphatic: subconjunctival lymphatics (afferent arm of immunologic reactions)
• Antibody: [IgA and IgG] peripheral = central cornea, [IgM] > periphery (larger
size restricts diffusion into the centre)
• Langerhans cells, the dendritic antigen presenting cells >periphery
• Mediator/complement/inflame cell: > antigen-antibody complexes, > effective
complement activation, >inflammatory cells/mediator attraction, > release
proteolytic and collagenolytic (destruction)
• Histologically, the peripheral cornea also contains a reservoir of inflammatory
cells including neutrophils, eosinophils, lymphocytes, plasma cells and mast cells .
• Clinical: prone to infections, hypersensitivity disorders, mass lesions and
degenerations may secondarily spread to involve the limbus and peripheral cornea
• more susceptible to alteration in a wide variety of infectious and non-infectious
systemic and local diseases, leading to a clinical entity termed Peripheral
Ulcerative Keratitis (PUK).

PUK: Activity vs Resolution
• Active: ED + stromal melting +
conj/sclera/episcleral inflam
• Conj: resolution of inflammation
• Epithelium: Epithelialization of the corneal
• Thickness: residual stable thinning
• Scar: residual stable vascularized scar

PUK Vs Mooren
• PUK without systemic association is known
as Mooren's ulcer and contributes to 31.5% of
PUK causes
• Mooren's ulcer occurs in the absence of
scleritis and is a diagnosis of exclusion, with a
distinctive overhanging edge.
• PUK Females are more likely to be affected
generally, although this is reversed for
Mooren ulcers.

Congenital/Inherited Corneal D/o

IC3D 2015 (International
Classification of Corneal
Dystrophies)
- Genetic (chromosomal/gene)
- Clinical (pattern/anatomical layer)
- Pathology (histo/biochem/confocal)

Staining- Others
-Macular CD (MPS/GAG):
colloidal blue (+ Alcian blue)
- Iron: Prussian blue
- Myelin: Lusol fast blue

FED
• medical management in the form of Rho
kinase inhibitors for endothelial regeneration,
hypertonic saline to deturgesce the cornea
and anti-glaucoma medications to decrease
endothelial stress.

● Endothelial cell counts less than 1000/mm2,
morning increase in corneal thickness, or the
presence of epithelial edema suggests that the
cornea may decompensate following
intraocular surgery

Hazy cornea @neonate
• STUMPED
• Sclerocornea (90% BL/non progressive)
• Tear in DM (traumatic labour/Haab striae
@congenital glaucoma- vertical vs horizontal)
• Ulcer (TORCHES)
• Mucopolysaccharidoses (Type 1H & 1S)
• Peter’s anomaly (80% BL)
• EndoT dystrophy CHED2 (AR at birth)
• Dermoid (limbal @Goldenhar)

Congenital/Dev Corneal Abn
Developmental Anomalies of cornea
• Abn Size/Shape/Structure
– Micro (<10), megalo (>12), absence, ant-megalopthalmos (iris-lens-CB-cornea)
– Cornea plana (flat/horizontal oval), sclerocornea
– Post keratoconus, ant staphyloma, post embryotoxon
• Hereditary Syndromes and Chromosomal Aberrations
– Ant Seg Dysgenesis esp Peter’s anomaly/ARS
– CD esp CHED II (AR)
– Metabolic dz esp MPS type 1H/1S
– Cong tumour esp limbal dermoid (Golderhar)
Secondary Abnormalities Affecting the Fetal Cornea
• Intrauterine Keratitis: Bacterial and Syphilitic
• Congenital Corneal Keloid
• Congenital Corneal Anesthesia
• Congenital Glaucoma (Haab’s striae horizontal DM rupture line)
• Birth Trauma (vertical DM rupture line)
• Arcus Juvenilis

Corneal Deposits- General
• DDX with anatomical layer
• DDX pigmented/non pigmented/crystalline
• DDX systemic association: drugs, metabolic/storage dz, mineral deposit
(Type 1H/Hurler
& 1S/ Scheie)

Corneal Degeneration
• Age-Related (Involutional) Changes
– Hassal Henle (hyaline @peripheral DM)
– Arcus senilis
– Hudson Stahll line (ferritin horizontal line @ central
cornea/epiT/>inf)
• Epithelial/Subepithelial/Ant stromal Degenerations
– Salzmann nodular
• Non inflam/>F
• a/w long standing keratitis/blepharitis/idiopathic
• gray white, flat-raised lesion @ eyelid-cornea contact/central
cornea (+irreg & thickened epiT/Bowman)
– Pannus= fibrovascular growth btw epiT-Bowman
– BandK
– Actinic/Solar/Labrador/Spheroidal keratopathy
• Solar irradiation  collagen elastotic degeneration 
spheroidal deposit (translucent brown coloured w basophilic
globules) @ superficial cornea/interpalpebral

Band Keratopathy
• Calcification/Ca plaque@ superficial/Bowman +-subepi/ant stroma @
interpalpebral fissure
• Chronic: mths to years, +- lucent hole (= nerve end)
• Ca & phosphate imbalance +- alkalosis
• Causes
– a/w chornic eye inflam/uveitis/surface dz or systemic high Ca
– Inflam: chronic uveitis (JIA/herpetic/IK/sarcoid)
– Systemic: hyperPTH/high vit D, renal dz/lupus/gout
– Surface: dry eyes, ocular injury (chemical), eye drops
• Others contributing factors
– SO with aphakia
– Intracameral rtPA
– Endothelial compromise
• Ix
– Ca/PO4, uric acid/PTH, RP/urine analysis, uveitis workup
• Management
– EDTA chelation/removal
– Superficial keratectomy: manual/PTK

retrocorneal fibrous membrane
(RCFM)
• Infiltration of polymorphonuclear leukocytes in
response to severe corneal injury can induce
endothelial cells to become fibroblastic and to
synthesize a retrocorneal fibrous membrane
(RCFM). RCFM forms between the Descemet
membrane and the corneal endothelium and
causes a significant decrease in visual acuity.
Unlike normal corneal endothelial cells, which
accumulate a limited amount of type I collagen
protein, the fibroblastic cells isolated from the
RCFM predominantly express type I collagen.

Medication & cornea
• Drug-Induced Deposition and Pigmentation
–Corneal Epithelial Deposits
–Stromal and Descemet Membrane Pigmentation
–Endothelial Manifestations
• Toxic Keratoconjunctivitis From Medications

Adrenochrome Pigmentation
• Oxidation of epinephrine  adrenochrome
 autooxidation  melanin release  brown
discolouration
• Epinephrine: antiglaucoma eyedrop
• Susceptible surface: ED/keratitis, acidic
environment

Crystalline K (Ifx vs non-ifx) & Vortex K
• Non-ifx
– Lipid deposit: Schnyders CD
– Mineral deposit: argyrosis (silver), Band K (calcium), Chrysiasis (gold)
– Protein deposit: cystinosis, dysproteinemia (multiple myeloma)
– Medication deposit (topical): gutt ciloxan
– Medication vortex K: amiodarone, tamoxifen, phenothiazines/chlorpromazine,
indomethacin, chloroquine + Fabry dz (ask ABCDE)
• Deposit @epiT/radiating below pupil axis/BL
– Idiopathic: crystalline dystrophy of Bietti
• Ifx
– Suboptimal inflam response to microb
• >gram +ve/rare/indolent/>strep viridans/epidermitis/fungi
• > post PK eye with long term topical steroid
– SSx: stromal opacities (branching/grey-white/slow progress)
– +- intact/ED, +- min inflam
– Rx: c&s, topical Ab (weeks)

Corneal Edema
• EndoT dysfx (barrier/pump)
• Causes
– Age
– IOP
– Post op (PBK/ABK)
• Phaco 4-10% cell loss /complicated/IOL touch/IOP
• Prevent: dispersive OVD, stable IOP, BSS plus (glutathione)
– Uveitis/inflam
– FED/PDS/PEX/KC with hydrops
• Signs
– EpiT: haze/microcyst/bullae
– Stroma: thicken/wrinkle (Waite-Beetham line)
– DM: fold
– EndoT: pseudo/gutta
– Post collagenous layer (retrocorneal membrane)
• Mx
– Hypertonic saline/pain relief/BCL
– EndoT transplant

Corneal decompensation (post op)
• lens: phakia/pseudophakia/ACIOL
• cornea: FED, endo/DM injury
• IOP: malignant glaucoma/suprachoroidal
hrge
• wound leak/hypotony/shallow AC

Descemet’s Detachment
• rhegmatogenous (tear), tractional, bullous and complex
detachments based on pathophysiology, clinical, ASOCT findings
and treatment required.
• Rhegmatogenous: a/w tear, free float undulating membrane,
instrument injury (phaco probe/IOL injector
• Bullous: a/w hydroseparation, intraop fluid wave/well defined
plana or convex detachment, stromal hydration/vision blue/OVD inj
(cannula too posterior)/
• Spontaneously resolve
• Intervention if: visual axis, pain/bullae, non resolve
• Pneumo-descemeto-pexy
• Relaxing descemetomy (keratome, bent 26G needle) + air
bubble/pneunodescemetopexy- more for bullous DD
• Venting incision- more for tear associated

AdenoV eye dz
• four distinct syndromes: pharyngoconjunctival fever
(PCF); epidemic keratoconjunctivitis (EKC); acute
nonspecific follicular conjunctivitis (NCF) and chronic
keratoconjunctivitis
• redness and keratitis, up to 20 uniform, subepithelial
corneal infiltrates (the hallmark of EKC) develop on day
11 and are most prevalent during the third and fourth
weeks of infection. Approximately 30 to 50 percent of
patients with EKC will de-velop these infiltrates, which
may contribute to persistent visual loss and light
sensitivity and necessitate long-term steroid therapy

• 4 times a day of topical 0.05% CsA
(Restasis®), in addition to the topical
corticosteroids they were using for the first 15
days, and then 2 times a day of topical 0.05%
CsA (Restasis®) after topical corticosteroids
were discontinued.

AC disorder (Cornea + Iris +- Glaucoma +- Lens)
• Iatrogenic
• Trauma
• Uveitis
• AC dysgenesis
• ICE syndrome
• Iridoschisis

Cornea Embryotoxon
• Anterior (=Arcus, deposit at stromal with clear limbal interval)
– senilis & juvenilis
– hyperlipidemia (lipodes/Schnyder CD)
– IK, sclerokeratitis, megalocornea
• Posterior (early termination of DM, advanced Schwalbe line)
– Normal/AD (20%)
– ARS
– Alagille syndrome (arteriohepatic dysplasia)
– X-linked ichthyosis
– familial aniridia.

Prominent Corneal Nerves
1. Ocular diseases:
• Keratoconus
• Infection (Acanthamoeba)
• Keratoconjunctivitis sicca
• Fuch’s endothelial dystrophy
• Congenital glaucoma
• Corneal Edema
• Trauma
2. Systemic diseases:
• Leprosy
• Neurofibromatosis
• MEN type 2b (medullary CA thyroid,
parathyroid CA, pheochromocytoma)
• Refsum’s disease, Riley-Day
• Ichthyosis
• Normal variant with increasing age

Normal Slit Lamp Examination
•Cornea
– KC @young pt + placido
– Vortex K @systemic drug/DDx
– Prominet corneal nerve @DDx
– Crystalline K @post PK
– KF ring @Wilson

Epithelial In-/Down-growth
• Epithelial migration (fr conj/cornea) to 
– intraocular structure/s (after penetrating ocular surgery/trauma)
– or corneal flap/stromal bed (after LASIK)
• Cells  fibrosis 
– Melting (collagenase release fr necrotic epiT)
– Inflam
– Astig/cover axis
• Probst/Machat EI classifications (>post LASIK)
– 1: 2cells thick/2mm fr flap (thin transparent, well delineated white line edge)
– 2: thicker/>/=2mm (rolled or grey edge)
– 3: >thick/>/=2mm (opaque-white-rolled edge-progress-flap melt)
• Fluorescein staining (epiT fistula)
• Mx (intraocular):
– En bloc excision + full thickness corneo-scleral graft
– Devitalised with cryoT or photocoagulation
– Intracameral 5FU or MMC
• Mx (LASIK flap):
– Grade 1- monitor weekly for 1mth  stable vs progression
– Lift & scrape +- ethanol/MMC/PTK with closure /tight suture/glue +- Nd-YAG

• Fibrovascular Downgrowth vs. Epithelial Downgrowth
• The term retrocorneal membrane can encompass both epithelial downgrowth and fibrous downgrowth. Both can be a result of trauma or
intraocular surgery; for example, fibrous downgrowth has been reported after cataract surgery[38], rigid Schreck anterior chamber lens
implantation[39], intraocular telescope implantation[40], and traumatic corneoscleral wound dehiscence.[41] Risk factors appear to be similar,
including prolonged inflammation, wound dehiscence, and delayed wound closure. Symptoms in each are nonspecific, and both appear as a
translucent retrocorneal membrane. Complications of fibrous downgrowth are like that of epithelial downgrowth, including glaucoma.[42] However,
there are a few distinctions. The membrane in fibrous downgrowth may be vascular and is predominately fibrous instead of cellular.[19][14] Fibrous
downgrowth is also more common than epithelial downgrowth and tends to progress more slowly. There are few adjunctive tests to confirm the
presence of fibrous downgrowth, although there are reports that immunohistochemical positive staining for α-smooth muscle actin can help sway
the diagnosis towards fibrous downgrowth.[43] However, management mainly appears to be similar between epithelial and fibrous downgrowth
with the use of photocoagulation, surgical excision, and intracameral metabolites. Bevacizumab has been suggested as a unique treatment for
fibrous downgrowth. Mansour reports using combined intracorneal (0.05 mL; 1.25 mg) and subconjunctival (0.1 mL; 2.5 mg) injections of
bevacizumab in a patient to halt vascularization within the fibrous membrane to reduce intraocular bleeding.[14] Intracorneal and subconjunctival
routes of injection were chosen instead of intracameral due to the presence of glaucoma and intravitreal silicone oil.
• Pseudophakic Bullous Keratopathy vs. Epithelial Downgrowth
• Pseudophakic bullous keratopathy (PBK) is the development of irreversible corneal edema after cataract surgery and postoperative
inflammation. This corneal edema occurs due to the loss of corneal endothelium secondary to surgical trauma. PBK can clinically resemble epithelial
downgrowth with a reduction in visual acuity, tearing, and pain. However, signs of PBK include stromal edema and sub-epithelial bullae. Epithelial
downgrowth should be considered in patients undergoing penetrating keratoplasty for presumed diagnoses of PBK, and these may be distinguished
immunohistochemically with the presence of anti-cytokeratin antibodies in epithelial downgrowth.[20]
• Epithelial Downgrowth vs. Secondary Endothelial Proliferation
• Secondary endothelization usually arises from ischemia and can also present after multiple intraocular surgeries. The endothelial cells can
proliferate in the angle and anterior surface of the iris. This can be considered a precursor to rubeosis iridis (neovascularization of the iris), which can
lead to neovascular glaucoma, a form of secondary glaucoma. Clinically, this can appear as neovascularization of the iris. Histologically, this can be
differentiated from epithelial downgrowth by a lack of stratification.[16]

• proliferating over the cornea, iris, trabecular
meshwork, ciliary body, crystalline/artificial
lens, vitreous body, and/or retina
• Glaucoma
• Endothelial dysfunction/cornea
decompensation

Dx
• Clinical: advancing edge, sheet like, scalloped border,
connection to wound
• sometimes appears as a cyst or as cells floating in the
anterior chamber.
• spot of argon laser photocoagulation is applied to
the area overlying the iris. If a membrane is present,
the laser spot will cause the tissue to blanch and
whiten, while laser applied to normal iris will result in a
sharp, darkened burn
• Aqueous aspiration and cytologic examination can
also be performed to assess for the presence of free
epithelial cells.

Intrastomal Blue-dye Injection
• Iatrogenic/inadvertent
• Toxic keratopathy w intraop edema, bluish
discolouration
• Resolved by 6wk (start 3/7 and near
resolved fully 2wk)
• DDx: DM detachment (deep stromal
separation)  need ASOCT to confirm
• Mx: postpone op in no view + ASOCT + gutt
steroid/Ab

AMT
• Intro: single epiT cell layer w BM, from human embryo sac (post
partum/ifx screen)
• Properties:
– Inert/no Ag-rejection/+substrate for cell growth/healing
(laminin/bioactin/GF)
– reduce scar/anti-inflam/anti angiogenesis/anti microbial
• Types: air-dry, glycerol preserved, fresh frozen
• IndiC: ocular (cornea & conj reconstruction), systemic
(wound/burn)
• Preop/postop
• Op: epithelial side up (for cell migration), side down (for anti
inflam), +- multilayer, inlay (cover defect area only, e side up),
overlay (cover large area as patch, e side up or down)
• Cx: disintegrate/necrosis/melt, ifx/contamination
• Limit: need normal stem cell/keratocyte to heal, need resolved
inflam/ifx
• Fresh frozen: price RM 1000+ (incl delivery fr HUSM, store -20,
expired 6/12), 097674039 (HUSM tissue bank)

AMT expanded IndiC
• corneal surface reconstruction
– PED
– Shield ulcer VKC
– total limbal stem cell deficiency (+limbal stem cell
transplantation)
• conjunctival substitute
– removal of pterygia, conjunctival lesions and
symblephara.
• substrate for ex vivo cultivation of limbal,
corneal and conjunctival epithelial cells

AMT Types
• cryopreserved (Cryo-AM) versus air-dried is
– cryo-AM >substrate for cultivating human limbal
epithelial cells increases release of wound-healing
mediators
• PROKERA®: Corneal Bandage
– PROKERA Slim: thinner ring to contour to the ocular
surface
– PROKERA Clear: retain visual acuity in the affected eye.
– PROKERA Plus: double layer for intense, sustained tissue
coverage

Omnigen AMT
• modified human amnion
• gamma-radiated and decellularised with
sodium dodecyl sulfate
• low heat vacuum dried amniotic membrane
without spongy layer
• efficient substates for the ex-vivo expansion
of limbal stem cells, and have certain
advantages but also some limitations such as
limited flexibility and early dissolution

Corneal Glue
• Intro: therapeutic/prophylactic
• IndiC: 1-2mm perforation, >temporary measure
• Equipment:
– glue (isobutyl cyanoacrylate)- in 1ml syringe/27G needle
– LA, skin biopsy punch/sterile plastic, cotton bud/occ CMC, BCL
• Technique:
– LA/take swab c&s/debridement
– +- AC reformation prior
– dry cornea
– cotton bud-occ CMC-plastic disc-glue complex (or simple drop
technique)
– BCL
• Cx
– glue related:
– in AC (cataract)
– lid (symblepharon)
– epiT defect
– failed glue

EDTA chelation
• Indication: symptomatic band K (vision or chronic surface d/o)
• Procedure:
– LA/topical
– Epithelial debridement: crescent/beaver blade, +- 20% alcohol in
well (40s)
– EDTA 0.5-3%: gutt/soaked in Weck-cel sponge (2-3min)
– Debride
– +-BCL/gutt Ab/steroid
• Other option: +-sup keratectomy +- AMT
• Causes of bank K:
– primary vs secondary (ocular vs systemic)
– esp preservative eyedrops, chronic ifx/inflam/ulcer, chemical, SO,
– CKD/Ca/phosphate level

How to order EDTA
(ethylenediaminetetracetic)
• EDTA 3% (in syringe/patient)
• For band keratopathy chelation
• Call pharmacist in charge Mr Ian 1/7 prior &
before 12noon (ext 5860 or 6701)
• Write a manual prescription slip to send
down to ward supply pharmacy (basement)

Superficial Keratectomy &
Diamond Burr
• The corneal epithelium around the pterygium remnant was
removed down to Bowman’s layer and residual pterygium tissue
was scraped by a crescent knife. Diamond burr polishing was then
performed to smooth the entire corneal surface. A handheld
battery-driven ophthalmic burr with a 3.3 mm diameter diamond-
dusted sphere was used to polish the corneal surface for
approximately 10–15 seconds. To avoid haze, mitomycin C (0.2
mg/mL) was applied for one minute with a Weck-Cel® sponge
(Beaver-Visitec International, Waltham, MA, USA) and the eye was
thoroughly irrigated with balanced salt solution. A soft bandage
contact lens was placed on the eye at the end of the procedure.
Postoperatively, the patient was instructed to instill a topical
steroid, a topical antibiotic, and artificial tears, each four times
daily, for one month after surgery. The contact lens was removed
five days after the procedure.

• multiple, even, circular movements, taking
care not to induce irregular topography by
pushing too hard or tarrying in one region too
long.

Terminology
• Punctate epithelial erosions (PEE)
• Punctate epithelial keratitis (PEK)
• Subepithelial infiltrates
• Superficial punctate keratitis (non-specific)
• Filamentous keratitis
• Epithelial edema/bullae
• Superficial neovascularization & pannus
• Infiltration/Ulceration/Melting
• Deep vascularization/lipid deposition
• Descemet fold/striae
• Descemetocele
• Descemet break (Haab striae)/acute hydrops

New in cornea/ant seg
• Corneal tomography
– Pentacam (oculus)
– Orbscan (B&L)
– Sirius (CSO)
– Galilei (Zeimer)
• ICRS
• CAIRS (corneal allogenic
intrastomal RS)
• epiT mapping for KC
– OCT RTvue (Optovue)
– VHF U/S Artemis
(ArcScan)
• Aberration
– higher/lower
–Lenticular/cornea
–Ref surgery WF guided
LASIK, KC/ectasia
• Tear imaging: OCT, fringe
interferometry
• Meibography:
fx/density/anatomy
• Mydriasert (conj insert
for dilatation)
• Intracameral moxifloxacin
0.5mg/0.1ml)

Corneal Imaging- New
• Biomechanical properties
• Corneal ectasia
• Scheimpflug
• Ocular response analyser ORA Reichert
• Corvis ST (corneal visualization Scheimpflug tech)
• VHF US Artemis ArcScan
• BAD D value
• Corvis Biomechanical Index (CBI)
• Tomographic Biomechanical Index (TBI)
• Amsler-Krumeich
• CLEK (collaborative Longitudinal Evaluation of keratoconus
• Brillouin microscopy imaging (longitudinal modulus/mechanical compressibility of tissue-
cornea/lens/sclera)
• Pre-Descemet endothelial keratoplasty (PDEK)
• Endoilluminator-assisted, S or F stamp, Moutsouris sign for DMEK
• Dysphotopsia- positive (glare/halo/starbursts) vs negative (dark shadow at periphery)

OCT for ant seg/cornea
• N cornea
• Pathological cornea
• Corneal transplant
– level of scar/pathology
– esp lamellar K
• Refractive surgery
• Phakic IOL
• IOL calculation
• Post op DM
detachment
• VS optical system/UBM-
longer time, difficult,
corneal clarity, behind iris
penetration
• Multimodal imaging:
UBM, AS-photo, confocal
microscopy,
topo/tomography
• Intraop OCT
• OCT A
• Ultra-high-resolution
OCT

Corneal Imaging- New
• Corneal ectasia: early changes @post cornea & thickness
• BFS/ enhanced
• CTSP
• Deviation of front, back, thickness...5Deviation
• Tomo vs topo of cornea
• Biomechanical profile
• Corvis CBI Pentacam BAD
• Topo -- tomo -- tomo + biomechanic
• Scheimpflug based tomo
• AUC in ophthal study
• Vinciguerra screening report

• Prednisolone acetate 0.12% Eye Drop (Pred Mild)
• Prednisolone acetate 1% Eye Drop (Pred Forte)
• Loteprednol Etabonate 0.5% Ophthalmic Suspension
(Lotemax)
• Dexamethasone Sod Phosphate 0.1% 0.5ml (Minims
Dexa)
• Dexamethasone Sod Phosphate 0.1% 5ml (Maxidex)
• Dexamethasone Poly B eye drop & ointment ?%
• Fluorometholone Ophth Suspension 0.1% (FML)

Cornea: Notes

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