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Orthokeratology (Ortho-K) - PG Exam Notes

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Definition

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Mechanism of Action

• Central corneal epithelial thinning (flattening of central cornea)
• Mid-peripheral stromal and epithelial thickening (due to hydraulic forces redistributing epithelial cells from center to mid-periphery)
• The net result: central cornea flattens by ~6 µm per 1.00 D of myopia correction
• Creates peripheral myopic defocus on the retina - this is the mechanism behind myopia control (retinal signal inhibits axial elongation)
• Effect onset: observable after 1 night of wear; stable after 1-2 weeks
• Effect is fully reversible on cessation of lens wear

How much correction?

• 6 µm of corneal flattening = 1.00 D reduction in myopia
• Since cornea accounts for 60% of the eye's focusing power, even minor epithelial redistribution significantly alters refraction

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Lens Design (4-Zone / 5-Zone Design)

• CRT lenses (3-zone): Base Curve, Return Zone Depth (RZD), Landing Zone Angle (LZA) - sagittal height-based fitting
• VST lenses (4-zone): Use continuous transitional arcs

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Ideal Fluorescein Pattern ("Bull's-Eye" Pattern)

• Central zone: Touch / bearing (dark - no fluorescein)
• Reverse/mid-peripheral zone: Bright ring of fluorescein clearance (pooling)
• Alignment zone: Peripheral alignment/landing (thin, even band)
• Edge: Adequate tear exchange clearance

• Central flattened treatment zone (bull's-eye center)
• Surrounding steepened reverse curve zone - must be centered within the pupillary circumference
• Centered reverse zone = effective peripheral defocus = better myopia control

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Indications

• Low to moderate myopia (up to -6.00 D)
• With-the-rule astigmatism up to -1.75 D
• Children and adolescents (primary use for myopia progression control)
• Adults who want to avoid spectacles/surgery during the day
• Athletes, swimmers, active lifestyle individuals
• Patients not suitable for refractive surgery (age <18, thin cornea)
• Mildly symptomatic dry eye (better tolerated than soft lenses)

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Contraindications

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Fitting Process

1. Corneal topography - map cornea surface (essential; determines lens parameters)
2. Keratometry - measure corneal curvature (K readings)
3. Refraction - determine target correction
4. Trial lens fitting - assess fluorescein pattern
5. Lens dispense + training - insertion/removal, hygiene education
6. Follow-up at 1 day, 1 week, 1 month, then every 3-6 months

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Efficacy for Myopia Control

• Reduces axial elongation by ~40-50% compared to spectacles
• 0.1 mm reduction in annual axial growth ≈ 0.25-0.30 D less myopia per year
• A 40-50% reduction in myopia progression can reduce lifetime risk of myopic maculopathy by 30-40%
• Recent Cochrane meta-analysis (Lawrenson et al., 2025 - PMID 39945354) confirms ortho-K as one of the most effective myopia control interventions in children

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Complications

Infective

• Microbial keratitis - most serious complication
  • Most common organism: Pseudomonas aeruginosa (gram-negative, aggressive)
  • Also: Acanthamoeba keratitis (from tap water exposure)
  • Risk higher in children due to hygiene compliance issues
  • Strict lens hygiene is mandatory

Non-infective

• Epithelial staining (superficial punctate keratitis) - most common minor complication
• Corneal infiltrates (sterile)
• Lens binding / adherence on waking
• Halos and glare (especially at night) - from optical zone edge effects
• Ghost images / monocular diplopia
• Over-correction or under-correction
• Corneal decentration of treatment zone
• Giant papillary conjunctivitis (GPC) - mechanical hypersensitivity

Fluorescein Staining Grading (Chu & Xie):

• Grade 0: No/minimal staining
• Grade I: Scattered punctate staining
• Grade II: Dense punctate + mild discomfort
• Grade III: Localized epithelial defects + moderate irritation
• Grade IV: Extensive epithelial defects + severe symptoms

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Comparison with Other Myopia Control Methods

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Key Exam Points (High-Yield)

1. Lens type: RGP (Rigid Gas-Permeable) lenses worn overnight - NOT soft lenses
2. Mechanism: Central epithelial thinning + mid-peripheral thickening via hydraulic forces
3. Fluorescein pattern: "Bull's-eye" = central touch + mid-peripheral clearance + peripheral alignment
4. Myopia limit: Effective up to -6.00 D; astigmatism up to -1.75 D
5. Most dangerous complication: Microbial keratitis (Pseudomonas aeruginosa)
6. Myopia control mechanism: Peripheral myopic defocus - mid-peripheral corneal steepening shifts peripheral retinal image focus anterior, reducing stimulus for axial elongation
7. Effect is reversible - distinguishes it from LASIK/PRK
8. Tool for fitting: Corneal topography (mandatory)
9. Stability: Achieved in 1-2 weeks; retainer lenses required to maintain effect
10. Primary target population: Children 6-18 years with progressing myopia
11. CRT (Paragon) and VST (BE Retainer) are the two main FDA-approved systems

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Recent Evidence

• Sartor et al. 2024 (PMID 38904856) - Systematic review + meta-analysis confirming benefits and quantifying risks of ortho-K
• Lawrenson et al. 2025 (PMID 39945354) - Cochrane living systematic review confirming ortho-K among top myopia control interventions
• Schmidt et al. 2025 (PMID 40219611) - Network meta-analysis comparing all myopia interventions in children

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Summary Mnemonic for Complications: "MICAH-G"

• M - Microbial keratitis (Pseudomonas, Acanthamoeba)
• I - Infiltrates (sterile)
• C - Corneal staining / epithelial SPK
• A - Adherence / binding of lens
• H - Halos and glare
• G - Giant papillary conjunctivitis

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Osteo-Odonto Keratoprosthesis (OOKP) - PG Exam Notes

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Definition

Simple exam definition: "A tooth-and-bone lamina used as a biological haptic to support a PMMA optical cylinder implanted into a blind eye, covered by buccal mucosa."

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Historical Background (High Yield)

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Why a Tooth?

• Biologically autologous - no rejection
• Dentin is biocompatible and resistant to resorption (compared to synthetic materials)
• Provides rigid structural support for the PMMA optic
• Natural cement/periodontal tissue integrates with surrounding ocular tissue
• Bioceramics are inferior: at low pH (infection/inflammation), they degrade faster than natural tooth/bone

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Indications

1. Stevens-Johnson Syndrome (SJS) / Toxic Epidermal Necrolysis (TEN) - most common indication
2. Ocular Cicatricial Pemphigoid (OCP)
3. Severe chemical burns (acid or alkali) - second most common
4. Trachoma (end-stage cicatricial)
5. Graft-vs-Host Disease (GVHD) affecting ocular surface
6. Multiple failed conventional corneal grafts
7. Bullous keratopathy post-glaucoma surgery
8. Severe dry eye with failed ocular surface reconstruction
9. Aniridia-related keratopathy

Key rule: Bilateral disease only - not indicated for unilateral disease

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Contraindications

Absolute Contraindications

• Age < 17 years
• No perception of light (NPL) - surgery will only harm
• Advanced glaucoma (already discussed separately in assessment)
• Irreparable retinal detachment
• Phthisis bulbi (high risk of losing residual perception of light)
• Active TB (systemic)
• Smoking and betel nut chewing (some centers)

Relative Contraindications

• Mentally unstable patients
• Defective light perception (may indicate advanced glaucoma)
• Unrealistic expectations (cosmetic or visual)
• Unable to commit to lifelong follow-up
• Systemic diseases adversely affecting wound healing

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Patient Assessment (Pre-operative)

1. Ophthalmological Assessment

• Full ocular history and examination
• Retinal function assessment - ERG, ultrasound B-scan (to confirm intact retina and optic nerve)
• Perception of light (PL) - must be present
• Intraocular pressure (IOP) - rule out advanced glaucoma (most common cause of MOOKP failure)
• Visual field (if possible)
• Fornix depth and lid status

2. Dental / Maxillofacial Assessment

• Tooth selection: mono-radicular tooth, preferably canine (longest root, single root)
  • Upper canine preferred
  • If no canine: premolar or central incisor
• Imaging: Orthopantomography (OPG), X-ray, cone-beam CT to evaluate root structure and alveolar bone
• If edentulous (no teeth): allograft considered (but worse outcomes due to HLA mismatch and laminar resorption)

3. Psychological Assessment

• Past years of poor sight - risk of psychopathology
• Realistic expectations regarding vision and cosmesis
• Ability to commit to lifelong follow-up
• Financial and emotional preparedness

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Surgical Procedure - Two-Stage Operation

Stage 1a - OOKP Lamina Preparation and Subcutaneous Implantation

1. Tooth extraction (canine + surrounding alveolar bone)
2. Lamina fabrication - tooth root trimmed to a lamina (disc-shaped plate) of dentin and bone
3. A hole is drilled in the center of the lamina
4. PMMA optical cylinder (the artificial optic) is fitted and cemented into the hole
5. The assembled tooth-PMMA complex is then implanted subcutaneously under the skin of the lower eyelid or infraorbital region (contralateral side or cheek)
   • Purpose: to allow vascularization of the lamina over 3-4 months
   • This is the "incubation" period

Stage 1b - Ocular Surface Preparation (can be concurrent or sequential)

1. Removal of diseased ocular surface: conjunctiva, corneal epithelium, Bowman's membrane
2. Full-thickness buccal mucosal graft (~3 cm diameter, muscle-free) harvested from the cheek
3. Mucosal graft sutured over the anterior ocular surface to create a stable mucosal barrier
4. Time allowed for graft healing (~3-4 months)

Stage 2 - Implantation (~4 months after Stage 1)

1. Retrieval of the vascularized OOKP complex from the subcutaneous site
2. Central trephination of the eye (removing central cornea)
3. Mucosal flap elevated (the buccal mucosa placed in Stage 1b)
4. OOKP complex inserted into the central corneal defect and sutured in place
5. Mucosal flap re-draped over the OOKP lamina (covers the tooth-bone-PMMA complex)
6. Only the PMMA optical cylinder protrudes through the center of the mucosa - this is the functional "window"

Key point for exams: The tooth-bone lamina is NOT placed directly; it is first incubated subcutaneously for vascularization - this is what makes OOKP survive long-term without rejection.

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Structure of the OOKP (What It Looks Like)

[Buccal Mucosa covering] → [Dentin-Bone Lamina (tooth)] → [PMMA Optical Cylinder protruding]
                                       ↕
                              [Eye / Corneal opening]

• The PMMA cylinder acts as the clear window/cornea
• The tooth lamina acts as the haptic (structural scaffold)
• The oral mucosa acts as the biological covering (replaces conjunctiva/cornea)

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Outcomes

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Complications

Maxillofacial / Surgical Complications

• Mandibular fracture
• Failed tooth extraction
• Fistula formation
• Maxillary sinus perforation
• Exposure of adjacent tooth root
• Oral mucosal flap perforation
• Paresthesia at implantation site
• Sinusitis / graft site infection

Mucosal Complications

• Mucosal graft defect
• Mucosal overgrowth (grows over optical cylinder - reduces vision)
• Mucosal necrosis / melting (most serious surface complication)
• Submucosal scarring

Ocular Complications

Exam high-yield: Glaucoma = most common cause of vision loss post-OOKP. Laminar resorption = most common cause of OOKP failure (structural).

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Comparison: MOOKP vs Boston KPro

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Multidisciplinary Team Required

• Ophthalmologist (corneal specialist)
• Maxillofacial / Oral surgeon (tooth extraction and lamina preparation)
• Radiologist (OPG, cone-beam CT)
• Psychologist (pre-operative counseling)
• Anesthesiologist

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Monitoring Post-Operatively

• Vision testing and visual fields
• CT scanning - standardized radiological CT monitoring of laminar integrity (longitudinal)
• Slit-lamp examination for mucosal health
• IOP monitoring (glaucoma surveillance)
• Watch for signs of laminar resorption, retinal complications

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Key Exam Points (High-Yield Summary)

1. "Tooth-in-eye" surgery - uses patient's own canine tooth + alveolar bone as scaffold
2. Invented by Strampelli (1963); modified by Falcinelli (MOOKP); standardized as Rome-Vienna Protocol (2001-2002)
3. Indication: bilateral end-stage ocular surface disease (SJS most common)
4. Optic material: PMMA (polymethyl methacrylate) cylinder
5. Tooth chosen: Canine (mono-radicular, longest root) - preferably upper canine
6. Stage 1a: OOKP assembled and incubated subcutaneously (cheek/lower eyelid) for ~4 months for vascularization
7. Buccal mucosa used: ~3 cm, full-thickness, muscle-free graft
8. Most common complication of vision loss: Glaucoma
9. Most common cause of structural failure: Laminar resorption (especially in SJS patients; associated with S. epidermidis)
10. Anatomic success at 18 years: ~85%
11. Gold standard KPro for end-stage disease: MOOKP > Boston KPro
12. If no tooth available: allograft used (worse outcomes - more laminar resorption due to HLA mismatch)
13. Contraindicated if no PL, advanced glaucoma, phthisis, age < 17 years
14. Vision improvement expected: 78% achieve 20/400 or better

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Mnemonic for Indications: "SJS-COT-GABS"

• S - Stevens-Johnson Syndrome
• J - (and TEN)
• S - Severe chemical burns
• C - Cicatricial pemphigoid (OCP)
• O - Other autoimmune (GVHD)
• T - Trachoma (end-stage)
• G - Grafts (multiple failed corneal grafts)
• A - Aniridia keratopathy
• B - Bullous keratopathy
• S - Severe dry eye

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Lamellar Keratoplasty - PG Exam Notes

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Definition

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Corneal Anatomy (Quick Revision - Essential Context)

1. Epithelium (~50 µm)
2. Bowman's layer (~12-15 µm) - acellular
3. Stroma (~500 µm) - 90% of corneal thickness
4. Pre-Descemet's Layer (PDL) / Dua's layer (~10 µm) - described 2013
5. Descemet's Membrane (DM) (~10-15 µm) - basement membrane of endothelium
6. Endothelium (~5 µm) - single cell layer

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Classification of Lamellar Keratoplasty

LAMELLAR KERATOPLASTY
│
├── ANTERIOR LAMELLAR KERATOPLASTY (ALK)
│   ├── 1. Bowman's Layer Transplant (BLT / BMT)
│   ├── 2. Superficial Anterior Lamellar Keratoplasty (SALK)
│   └── 3. Deep Anterior Lamellar Keratoplasty (DALK)  ← Gold Standard ALK
│
└── POSTERIOR LAMELLAR KERATOPLASTY (PLK) / Endothelial Keratoplasty (EK)
    ├── 4. DSEK (Descemet's Stripping Endothelial Keratoplasty)
    ├── 5. DSAEK (Descemet's Stripping Automated EK)  ← Most widely performed
    ├── 6. DMEK (Descemet's Membrane EK)  ← Best visual outcomes
    ├── 7. PDEK (Pre-Descemet's Endothelial Keratoplasty)
    └── 8. DMAEK (Descemet's Membrane Automated EK)

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ANTERIOR LAMELLAR KERATOPLASTY (ALK)

1. Bowman's Layer Transplant (BLT / BMT)

• Isolated Bowman's layer (~12-15 µm) is harvested from donor cornea and transplanted onto a prepared recipient bed
• Does NOT involve any biological cellular tissue (Bowman's is acellular) - hence NO RISK OF ALLOGRAFT REJECTION
• Originally described for post-PRK subepithelial scarring

• Keratoconus - to flatten the cornea and improve contact lens fit/retention, slowing progression
• Arrest of keratoconus progression - delaying or avoiding need for DALK/PK
• Post-refractive surgery subepithelial haze (post-PRK)

• Bowman's layer peeled from donor corneoscleral disc
• Recipient corneal surface prepared (epithelium removed)
• Donor Bowman's layer laid on recipient surface

• No rejection risk (acellular)
• Does not restore vision dramatically - improves corneal biomechanics and CL fit
• Experience is limited compared to DALK
• Prepared with microkeratome or femtosecond laser

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2. Superficial Anterior Lamellar Keratoplasty (SALK)

• Partial-thickness excision of corneal epithelium + superficial stroma
• Endothelium, Descemet's membrane, and deep stroma are retained
• Donor tissue: corresponding superficial partial-thickness graft

• Opacification of the superficial one-third of corneal stroma NOT caused by potentially recurrent disease
• Marginal corneal thinning or infiltration: recurrent pterygium, Terrien marginal degeneration, limbal dermoid, other tumours
• Localized thinning or descemetocoele formation

• No risk of endothelial rejection
• Less invasive than DALK or PK
• Endothelial quality in donor irrelevant

• Depth of dissection limited - cannot reach deep opacities
• Interface haze may compromise vision

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3. Deep Anterior Lamellar Keratoplasty (DALK)

• Corneal tissue removed almost to the level of Descemet's membrane
• Endothelium and DM are left in situ (not transplanted)
• Because endothelium is the major target for rejection, no risk of endothelial rejection
• Gold standard for anterior lamellar keratoplasty

• Disease involving the anterior 95% of corneal thickness with normal endothelium
• Absence of breaks or scars in Descemet's membrane
• Keratoconus (without history of acute hydrops) - most common indication
• Superficial trauma with corneal opacification
• Chronic inflammatory disease (e.g., atopic keratoconjunctivitis) - increased rejection risk with PK
• Stromal dystrophies (Granular, Lattice, Macular dystrophy)
• Post-infectious corneal scars (healed bacterial/viral keratitis)
• Chemical injury with intact endothelium (see Fig. 8.8, Kanski's)

• Air injected via 27G needle into deep stroma at ~90% depth
• Type 1 bubble: cleavage at pre-Descemet's / PDL level
• Type 2 bubble: cleavage within Descemet's membrane itself - risk of perforation
• Ideal: Type 1 bubble giving maximum depth with intact DM

• No risk of endothelial rejection (epithelial/stromal rejection may still occur)
• Less astigmatism than PK
• Structurally stronger globe than PK
• Increased donor availability - endothelial quality irrelevant
• Can be converted to PK if DM perforates

• Difficult and time-consuming with high risk of perforation
• Interface haze may limit final best corrected visual acuity
• Visual outcome not quite equal to PK in all cases
• Significant surgeon learning curve

• Intraoperative DM perforation (→ convert to PK)
• Interface haze
• Stromal/epithelial rejection (not endothelial)
• Double anterior chamber (if DM perforates)

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POSTERIOR LAMELLAR KERATOPLASTY (PLK) / Endothelial Keratoplasty (EK)

• Fuchs' endothelial corneal dystrophy (most common)
• Pseudophakic/Aphakic bullous keratopathy (post-cataract surgery endothelial failure)
• Failed previous corneal graft
• Posterior polymorphous dystrophy
• Iridocorneal endothelial (ICE) syndrome

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4. DSEK (Descemet's Stripping Endothelial Keratoplasty)

• Host DM and endothelium stripped out using a Sinskey hook or specialized stripper
• Donor tissue: posterior stroma + DM + endothelium, manually cut
• Inserted as a "taco fold" through 5 mm incision
• Held in place by air bubble in anterior chamber

• Small incision - less astigmatism
• No sutures on cornea
• Faster visual recovery
• Lower rejection risk

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5. DSAEK (Descemet's Stripping Automated Endothelial Keratoplasty)

• Same as DSEK but donor tissue prepared with automated microkeratome for uniform thickness
• Graft inserted as taco-fold or scroll through ~5 mm incision
• Air bubble in AC holds graft against host stroma
• Patient lies supine post-op to allow bubble to tamponade graft

• More uniform graft thickness
• Better reproducibility
• Eye bank can pre-cut tissue

• Small incision (~5 mm vs full trephination)
• No or minimal sutures
• Faster visual recovery (1-3 months)
• Lower rejection rates
• More rapid rehabilitation

• Significant learning curve
• Specialized equipment required
• Visual outcome suboptimal vs DMEK due to stromal interface
  • Causes: graft thickness variation, graft irregularities, high-order aberrations, donor-recipient interface fibrosis
• Endothelial rejection can still occur
• Graft dislocation in early post-op period
• Requires patient to remain supine post-op

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6. DMEK (Descemet's Membrane Endothelial Keratoplasty)

• Developed by Gerrit Melles (2006)
• Only DM and endothelium transplanted - ultra-thin graft
• Host DM + endothelium stripped; donor DM + endothelium rolled into a scroll and injected via small incision (~3 mm)
• Graft unscrolled in AC using tapping/air maneuvers
• Air bubble (20% SF₆ gas) used to support graft

• Best visual outcomes of all EK procedures - clearest interface
• Fastest visual recovery (1-2 weeks for initial clarity)
• Lowest rejection rates of all corneal transplants (graft is almost acellular except endothelium)
• No donor stromal tissue = less interface irregularity, less HOA
• Better refractive predictability

• Most technically demanding EK procedure - steep learning curve
• Graft is only ~10-15 µm - extremely fragile, difficult to handle
• Higher risk of rebubbling (graft detachment requiring repeat air injection)
• Higher risk of primary graft failure (graft destroyed during preparation/insertion)
• Tissue wasted if preparation fails in OR

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7. PDEK (Pre-Descemet's Endothelial Keratoplasty)

• Developed by Agarwal (2013-2014) - based on discovery of Dua's layer
• Donor tissue: PDL + DM + endothelium harvested using Type 1 bubble technique (air injected into stroma to create cleavage at PDL level)
• PDL provides structural support to the otherwise fragile DMEK scroll
• Easier to handle than DMEK due to the added PDL scaffolding

• Easier to prepare and handle (less fragile than pure DMEK)
• Similar optical clarity to DMEK (minimal stromal content)
• Lower rebubbling rates than DMEK
• Can use younger donor tissue (easier to scroll/unscroll)
• Interface same quality as DMEK

• Thinner graft → better visual outcomes (approaching DMEK quality)
• Less interface haze

• Relatively newer - less long-term data
• Requires specialized PDEK clamp
• Type 1 bubble creation can be technically difficult

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8. DMAEK (Descemet's Membrane Automated Endothelial Keratoplasty)

• A modification of DMEK (described 2009) where a peripheral rim of stroma is retained at the edge of the donor tissue
• Provides a handling rim → easier to manipulate than pure DMEK scroll
• Combines DMEK optical quality with DSAEK ease of handling

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Comparison Table: All EK Procedures

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Comparison: ALK vs EK vs PK

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Key Exam High-Yield Points

1. Lamellar = partial thickness (vs Penetrating = full thickness)
2. DALK = Gold standard for anterior LK - uses Big Bubble (Anwar) technique
3. DALK indication: Keratoconus with normal endothelium and no DM breaks - most common
4. DALK advantage: No endothelial rejection risk; more donor tissue available (endothelial quality irrelevant)
5. DSAEK = most widely performed EK worldwide; automated microkeratome for donor prep
6. DMEK = best visual outcomes + lowest rejection; but most technically difficult
7. PDEK = PDL + DM + Endo; easier than DMEK; introduced by Agarwal
8. Bowman's transplant = no rejection risk (acellular tissue); used in keratoconus
9. Air bubble used post-operatively in ALL EK procedures to hold graft - patient must remain supine
10. SF₆ (20%) gas used in DMEK for graft tamponade
11. Endothelial rejection can still occur in DSAEK/DMEK but much lower than PK
12. DSAEK disadvantage: Interface haze due to donor stroma → suboptimal vision vs DMEK
13. DMEK rebubbling (graft detachment + re-injection of air) = most common post-op intervention
14. Fuchs' dystrophy = most common indication for EK procedures
15. In DSEK/DSAEK: graft interface = donor stroma → host pre-DM or host DM In DMEK: graft interface = donor DM → host pre-DM (cleanest interface = best vision) In PDEK: graft interface = donor PDL → host PDL (always PDL-to-PDL)

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Mnemonic: "Layers Replaced" (Posterior to Anterior)

• DMEK = D+E only (DM + Endothelium) - thinnest, best vision
• PDEK = P+D+E (PDL + DM + Endo) - slightly thicker, easier
• DSAEK = S+D+E (Stroma + DM + Endo) - thickest EK, most common
• DALK = Everything down to DM (but NOT DM itself) - anterior disease

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Orthokeratology (Ortho-K) - Explained Simply for PG Students

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Start With the Core Idea

Simple analogy: Think of it like wearing tight shoes overnight that reshape your feet by morning - except here, the "shoe" is a precisely engineered lens, and the "foot" is your cornea.

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Why Does Myopia Happen? (Quick Background)

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What Makes Ortho-K Lenses Different From Regular Contact Lenses?

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Anatomy of the Ortho-K Lens (4 Zones)

[CENTER] ← Zone 1: Base Curve (flat)
           ↓
           Zone 2: Reverse Curve (steep - the KEY zone)
           ↓
           Zone 3: Alignment Curve (matches peripheral cornea)
           ↓
[EDGE]  ← Zone 4: Peripheral Curve (edge lift)

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The Mechanism: Step by Step (with Reason for Each Step)

Step 1: Patient Inserts the Lens at Bedtime

• The eye is still → lens stays centred
• Closed eye creates a sealed chamber for hydraulic forces to work
• 6-8 hours of wear time is needed for sufficient epithelial redistribution

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Step 2: Hydraulic (Fluid) Forces Are Generated Under the Lens

• Under the flat Base Curve (Zone 1) → tear film is thin → creates positive pressure on the central cornea
• Under the Reverse Curve (Zone 2) → a deep tear reservoir forms → creates negative pressure in the mid-peripheral zone

Analogy: Think of the lens as a suction cup placed on the cornea. The center pushes inward; the ring around it sucks outward.

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Step 3: Central Corneal Epithelial Thinning

• A -3.00 D myope needs ~18 µm of epithelial thinning centrally - easily achievable overnight

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Step 4: Mid-Peripheral Epithelial Thickening

• Central flat zone (thinned epithelium)
• Mid-peripheral steep ring (thickened epithelium)

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Step 5: The Cornea is Now Reshaped by Morning

• Central cornea is flatter → reduces myopic power
• Mid-peripheral cornea is steeper → creates peripheral myopic defocus (crucial for myopia control)

• Bull's-eye pattern = central flat island + surrounding steepened ring
• This is the ideal, desired treatment zone

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Step 6: The Patient Removes Lenses in the Morning and Sees Clearly

• The epithelium holds its redistributed shape for 12-16 hours (sometimes up to 24 hours with established treatment)
• The Descemet's membrane, stroma, and endothelium are completely unaffected

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Step 7: Retainer Lens Phase (After 2 Weeks)

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BONUS: How Does Ortho-K Control Myopia Progression? (The Defocus Theory)

SPECTACLES:        Central focus on retina ✓
                   Peripheral focus BEHIND retina → "Grow longer!" signal → Myopia worsens

ORTHO-K:           Central focus on retina ✓
                   Peripheral focus IN FRONT of retina → "Stop growing!" signal → Myopia controlled

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What the Fluorescein Pattern Shows (and Why)

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Why RGP (Rigid Gas-Permeable) Lenses and Not Soft Lenses?

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Timeline of Effects

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The Most Dangerous Complication - and Why It Happens

1. Overnight wear = more hours on the eye = less tear exchange = more bacterial colonisation time
2. Central bearing (lens touching central cornea) = micro-trauma to central epithelium = breach in epithelial barrier = entry point for bacteria
3. Reverse geometry creates stagnant tear pool under the reverse curve = bacteria can colonise this reservoir
4. Paediatric patients (the primary Ortho-K population) = poorer hand hygiene compliance

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Summary in 10 Lines (To Write in Exams)

1. Orthokeratology uses overnight RGP lenses with a reverse geometry design to temporarily reshape the cornea.
2. The lens has 4 zones: Base curve (flat) → Reverse curve (steep) → Alignment curve → Peripheral curve.
3. Mechanism: Reverse geometry creates differential hydraulic pressure in the tear film under the lens.
4. Positive pressure under the base curve → central epithelial thinning (flattening).
5. Negative pressure under the reverse curve → mid-peripheral epithelial thickening (steepening).
6. 6 µm of central flattening = 1.00 D of myopia correction.
7. Effect appears after 1 night, stabilises in 1-2 weeks.
8. Effect is fully reversible - cornea returns to baseline in 48-72 hours on stopping.
9. Myopia control is achieved by peripheral myopic defocus (mid-peripheral steepening signals "stop growing" to the retina) - slows axial elongation by 40-50%.
10. Most dangerous complication = microbial keratitis (Pseudomonas) due to overnight wear + epithelial microtrauma.

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Stem Cells in Ophthalmology - PG Exam Notes

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Introduction

1. Self-renew (make more stem cells)
2. Differentiate into specialised daughter cells

• Immune privilege (less rejection)
• Surgical accessibility
• Easy monitoring by imaging (OCT, fundus photography)
• Small volume needed (few cells can make a big difference)

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Types of Stem Cells Used in Ophthalmology

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PART 1: STEM CELLS IN CORNEAL DISEASE (ANTERIOR SEGMENT)

A. Limbal Stem Cells (LSCs) - Most Important for Exams

Where Do They Live?

What Do They Do?

LSC (Stem cell) → Transient Amplifying Cells (TAC) → Post-mitotic cells → Terminally differentiated squamous cells
(at limbus)        (basal epithelium)                  (wing cells)          (surface cells)

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B. Limbal Stem Cell Deficiency (LSCD)

Causes

• Chemical burns (alkali > acid) - most common
• Stevens-Johnson Syndrome (SJS)
• Ocular Cicatricial Pemphigoid (OCP)
• Trachoma
• Multiple surgeries / cryotherapy
• Contact lens overwear
• Aniridia (PAX6 mutation)
• Idiopathic

Classification

• Unilateral - one eye affected (other eye is potential donor)
• Bilateral - both eyes affected (cannot use own eye as donor → need allograft or alternative source)

Signs of LSCD (Kanski's):

1. Conjunctivalization of cornea with goblet cells - confirmed with:
   • Confocal microscopy
   • Impression cytology with PAS (Acid Schiff) stain
   • Monoclonal antibody against Cytokeratin 19 (conjunctival marker)
2. Superficial and deep corneal vascularization
3. Fibrovascular pannus
4. Persistent epithelial defects
5. Scarring
6. Symptoms: reduced vision, dryness, redness, photophobia, blepharospasm, pain, symblepharon

Key concept: Conjunctivalization = conjunctival epithelium grows over the cornea (because there are no limbal cells to maintain the corneal border). Goblet cells on the cornea confirm this (normal cornea has NO goblet cells).

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C. Treatment of LSCD - Surgical Options

Step 1: Treat all associated abnormalities first

• Lid disease, trichiasis, symblepharon, IOP, dry eye

Medical management (LSCD):

• Preservative-free lubricants
• Autologous serum drops (20% QID)
• Short course topical steroids
• Punctal occlusion

Surgical options (based on whether unilateral or bilateral):

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1. CLAU - Conjunctival Limbal Autograft

• Used for: Unilateral LSCD
• Tissue: Limbal tissue taken from the healthy fellow eye of the SAME patient
• Small biopsy (~2 clock hours) from healthy limbus transplanted to affected eye
• Advantage: No rejection (autologous)
• Disadvantage: Risk to the healthy donor eye; only 1-2 clock hours can be safely taken

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2. CLET - Cultivated Limbal Epithelial Transplantation

• Used for: Unilateral OR bilateral (small amount of tissue expanded in lab)
• Principle: Small limbal biopsy (1-2 mm²) is taken → cells cultured ex vivo on amniotic membrane or fibrin scaffold for 2-3 weeks → sheet of cells transplanted onto diseased eye
• Advantage: Large sheet from tiny biopsy; minimal donor site morbidity; suitable for bilateral disease (limited tissue from less-affected eye)
• Substrates: Human amniotic membrane (most common), fibrin gel, contact lens
• Disadvantage: Needs GMP laboratory, cell culture expertise, expensive

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3. SLET - Simple Limbal Epithelial Transplantation

• Used for: Unilateral LSCD (especially chemical burns)
• Technique (described by Sangwan, 2012):
  1. Small limbal biopsy (2 clock hours) from healthy fellow eye
  2. Amniotic membrane laid on recipient cornea (sutured/glued)
  3. Tiny pieces of limbal tissue placed directly on the amniotic membrane on the eye (no lab culture needed)
  4. Soft bandage contact lens placed over to hold everything
  5. Stem cells migrate and proliferate in vivo (on the patient's own eye)
• Advantage: No laboratory needed - can be done in any standard operating theatre; simpler than CLET; similar outcomes to CLET
• Disadvantage: Only for unilateral cases (needs a healthy donor eye)

Exam key: SLET = in vivo expansion (on the patient's eye); CLET = ex vivo expansion (in the laboratory)

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4. LSCT - Limbal Stem Cell Transplantation (Allogeneic)

• Used for: Bilateral LSCD (no usable tissue from either eye)
• Tissue source: Living related donor OR cadaveric donor
• Disadvantage: Needs systemic immunosuppression (to prevent rejection)
• Types:
  • Keratolimbal Allograft (KLAL) - cadaveric full-limbal ring
  • Living-Related Conjunctival Limbal Allograft (lr-CLAL) - from family member

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5. Oral Mucosal Epithelial Transplantation (OMET / COMET)

• Used for: Bilateral LSCD where limbal tissue unavailable (SJS affecting both eyes AND mouth may also be involved - use cautiously)
• Source: Buccal mucosa cells cultured on amniotic membrane
• Advantage: Autologous, abundant source, no rejection
• Disadvantage: Oral mucosa cells are NOT true limbal stem cells → conjunctivalization pattern may recur; goblet cells from oral mucosa can colonize cornea

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6. iPSC / ESC-derived Limbal Cells

• Research stage: Patient skin cells → iPSC → corneal epithelial cells
• Potential unlimited supply of autologous cells
• CALEC trial (NIH-sponsored): First human clinical trial of Cultivated Autologous Limbal Epithelial Cell (CALEC) graft - ongoing

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D. Corneal Stromal Stem Cells (CSSCs / Keratocyte Progenitors)

• Located in the anterior limbal stroma
• Have MSC-like properties
• Can differentiate into keratocytes (corneal stromal cells)
• Used for:
  • Corneal stromal regeneration (replacing scar tissue)
  • Supporting epithelial healing
  • Anti-inflammatory effects
• Phase 1 trials completed in India, Spain, China - promising results

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PART 2: STEM CELLS IN RETINAL DISEASE (POSTERIOR SEGMENT)

Why the Retina is a Good Target

• Immune privilege (blood-retinal barrier)
• Accessible via vitreoretinal surgery
• Easy monitoring with OCT, electroretinography
• Diseases well-characterised (AMD, RP, Stargardt)
• Small cell numbers needed (~50,000 RPE cells per macular area)

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A. RPE Replacement Therapy

Target diseases: Dry AMD, Stargardt Disease, Best Dystrophy

• Phagocytosing outer segment discs
• Transporting nutrients to photoreceptors
• Recycling visual pigments (visual cycle)
• Maintaining blood-retinal barrier

Stem Cell Sources for RPE:

Methods of Delivery:

1. Cell suspension - injected subretinally (simplest)
2. Polarised RPE monolayer patch - on a biodegradable scaffold (parylene, Bruch's membrane substitute)
   • Maintains correct polarity and function of RPE
   • Reduces risk of clumping

Key Clinical Trials:

• London Project to Cure Blindness (da Cruz et al.): hESC-derived RPE patch subretinally in wet AMD → improved visual acuity, no rejection/tumour at 12 months
• ACT (Advanced Cell Technology) Trials: hESC-derived RPE (MA09-hRPE) in Stargardt disease and dry AMD - Phase 1/2 safety data encouraging
• NEI iPSC-RPE Trial: Autologous iPSC → RPE patch for dry AMD (ongoing)

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B. Photoreceptor Replacement Therapy

Target diseases: Retinitis Pigmentosa (RP), advanced AMD

• More complex than RPE replacement (photoreceptors must form synaptic connections with bipolar cells)
• Sources: iPSC-derived photoreceptor precursors, Retinal Progenitor Cells (RPCs)
• Challenge: cells must migrate, integrate, and form functional synapses
• Still largely preclinical; some Phase 1 trials

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C. Neuroprotective Stem Cell Therapy (MSCs for Retina)

• Bone Marrow-derived MSCs (BM-MSCs) injected intravitreally or subretinally
• Do NOT replace photoreceptors directly - act by:
  • Releasing trophic/neuroprotective factors (BDNF, CNTF, VEGF)
  • Anti-inflammatory effects
  • Reducing oxidative stress
• Used in RP, AMD, diabetic retinopathy, optic neuropathy
• SCOTS (Stem Cell Ophthalmology Treatment Study): BM-MSCs in RP, Stargardt, AMD, optic nerve disease - phase 1/2, some visual improvement reported

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D. Retinal Ganglion Cell Replacement (Glaucoma)

• RGC loss in glaucoma is irreversible
• Stem cell strategies:
  • Neural Stem Cells (NSCs) or iPSC-derived RGC precursors
  • Challenge: RGC axons must grow through optic nerve → brain (long distance)
  • MSC neuroprotection: Preserving surviving RGCs via trophic support
• Mostly preclinical

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PART 3: STEM CELLS IN GLAUCOMA - TRABECULAR MESHWORK

• Trabecular Meshwork Stem Cells (TMSCs) identified in Schlemm's canal region
• TM cells maintain aqueous outflow; dysfunction → elevated IOP
• TM cell transplantation: Repopulate dysfunctional TM → restore aqueous outflow → lower IOP
• MSC injection into AC: Cells home to TM, reduce IOP in animal models
• Clinical trials: Early phase, promising animal data

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PART 4: STEM CELLS FOR LENS REGENERATION

• Lens Epithelial Stem/Progenitor Cells (LECs) exist at the equatorial lens epithelium
• After cataract removal, these cells can be stimulated to regenerate a lens
• Lin et al. (2016): In human infants with congenital cataract, lens capsule preserved after careful extraction → LECs regenerated a functional lens in 3 months
• Limitations: Works best in young patients; requires specific surgical technique preserving the capsule

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PART 5: STEM CELLS IN DRY EYE DISEASE

• MSCs from bone marrow or adipose tissue: Reduce inflammatory cytokines in lacrimal gland
• Lacrimal gland progenitor cells: For aqueous deficiency dry eye
• Still research stage

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Summary Table: Stem Cells in Ophthalmology

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High-Yield Exam Points

1. First ocular stem cell therapy: Kenyon & Tseng (1989) - limbal tissue transplantation
2. LSC location: Basal epithelium at limbus in Palisades of Vogt
3. Hallmark of LSCD: Conjunctivalization (goblet cells on cornea, confirmed by cytokeratin 19 / PAS impression cytology)
4. SLET vs CLET: SLET = in vivo expansion (no lab needed); CLET = ex vivo expansion (needs GMP lab)
5. SLET = introduced by Sangwan (2012) - revolutionised treatment of chemical burns
6. Bilateral LSCD: Cannot use fellow eye; options = allograft (needs immunosuppression) OR oral mucosal epithelium OR iPSC/ESC-derived cells
7. Kanski's tip: "In patients with unilateral involvement in SJS and OCP, donor tissue should NOT be taken from the unaffected eye" (risk of inducing LSCD in healthy eye)
8. RPE is primary target for retinal stem cell therapy (AMD, Stargardt)
9. hESC-derived RPE patch (London Project) - phase 1 showed no rejection, improved VA in AMD
10. iPSC advantage: Patient's own cells → no rejection risk (autologous); can be gene-corrected with CRISPR before transplantation
11. MSCs act via paracrine/trophic effects, NOT direct cell replacement (in retina)
12. Eye's immune privilege = less rejection due to blood-retinal barrier + immunosuppressive microenvironment → ideal for allograft stem cell therapy
13. Trabecular meshwork stem cells → glaucoma treatment (restoring aqueous outflow)
14. Lens regeneration: LECs + capsule preservation → functional lens regeneration (especially in neonates/infants)
15. iPSC-CRISPR pipeline: iPSC harvested from blood → CRISPR corrects gene mutation → differentiated into RPE → transplanted subretinally (future of personalised therapy)

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Mnemonic: "CLEAR SLET Makes RPE"

• C - CLET (Cultivated Limbal Epithelial Transplantation - ex vivo)
• L - LSCT (Limbal Stem Cell Transplant - allograft for bilateral)
• E - ESC (Embryonic Stem Cells - RPE, photoreceptors)
• A - Autologous CLAU (Conjunctival Limbal Autograft - unilateral)
• R - Retinal Progenitor Cells (RP treatment)
• S - SLET (Simple Limbal Epithelial Transplant - in vivo, no lab)
• L - Lens Epithelial Cells (lens regeneration)
• E - iPSC (induced Pluripotent - autologous, all tissues)
• T - Trabecular Meshwork SCs (glaucoma)
• Makes - Mesenchymal SCs (paracrine neuroprotection)
• RPE - RPE replacement (primary target in AMD/Stargardt)

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Orbital Exenteration - PG Exam Notes

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Definition

Distinguish from:

• Evisceration: Removal of intraocular contents only; scleral shell left intact
• Enucleation: Removal of the globe only; orbital fat, muscles, eyelids retained
• Exenteration: Removal of globe + all orbital soft tissues ± eyelids ± orbital bones

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Classification / Types

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Indications

A. Malignant Tumours (Most Common - ~85-90% of cases)

Eyelid / Periorbital Malignancies (Most common overall cause)

• Sebaceous gland carcinoma - pagetoid spread, field cancerization, most likely eyelid tumour needing exenteration
• Squamous cell carcinoma (SCC) - aggressive type with perineural invasion
• Basal cell carcinoma (BCC) - medial canthal / deeply invasive, radiation-resistant types
• Merkel cell carcinoma (rare, aggressive)
• Malignant melanoma of eyelid

Conjunctival Malignancies

• Conjunctival squamous cell carcinoma - when invading orbit
• Conjunctival malignant melanoma - with deep orbital invasion

Intraocular Malignancies with Extraocular Extension

• Uveal melanoma with extrascleral extension
• Retinoblastoma - massive extraocular spread (especially in delayed/neglected cases)

Primary Orbital Malignancies

• Adenoid cystic carcinoma of lacrimal gland - most common primary lacrimal gland malignancy; notorious for perineural spread; poor prognosis
• Rhabdomyosarcoma (in children) - when chemotherapy/radiation fails
• Orbital sarcomas
• Lymphoma (rare - usually responds to radiation)

Secondary/Metastatic Orbital Invasion

• Tumour invading orbit from:
  • Paranasal sinuses (maxillary, ethmoid, frontal sinus carcinoma)
  • Nasopharyngeal carcinoma
  • Intracranial tumours

Kanski's Note: "Orbital malignancy, either primary or where a tumour has invaded the orbit from the eyelids, conjunctiva, globe or adnexa when other forms of treatment have a very poor chance of success."

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B. Non-Malignant Indications (Rare)

• Mucormycosis (Rhino-orbital-cerebral mucormycosis) - most important non-malignant indication
  • Life-threatening invasive fungal infection in immunocompromised / diabetic patients
  • When antifungal therapy fails to control orbital invasion
  • Emergency/urgent surgery to prevent intracranial spread
• Invasive aspergillosis - similar indication
• Orbital tuberculosis with bony destruction (rare)
• Radiation necrosis causing uncontrollable pain/infection (palliative)
• Neglected orbital trauma with uncontrolled infection

Key exam fact: Mucormycosis is THE classic non-malignant indication - look for diabetic ketoacidosis patient with black eschar, proptosis, facial pain, black necrotic tissue

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Pre-operative Assessment

1. Imaging:
   • MRI orbit (better soft tissue detail, perineural spread)
   • CT scan (bony involvement, sinus extension)
   • CT chest/abdomen for distant metastasis
2. Biopsy - confirm diagnosis histologically
3. Ophthalmological assessment - is vision salvageable? Is exenteration truly necessary?
4. MDT discussion - ophthalmologist, oncologist, maxillofacial surgeon, neurosurgeon, prosthetist, psychologist
5. Psychological counselling - patient must understand permanent loss of eye, significant cosmetic deformity
6. Assessment of fellow eye - must document
7. Fitness for general anaesthesia - major surgery

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Surgical Procedure

Anaesthesia

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TYPE 1: Lid-Sparing (Subtotal) Exenteration

1. Marking: Incision marked 2 mm behind the ciliary margin of both lids (preserving lid skin)
2. Traction sutures: 2-3 sutures through upper and lower tarsi for traction on orbital contents
3. Skin incision: Made along marked area (radiofrequency probe / No.15 blade / cutting diathermy) circumferentially 360°
4. Skin and orbicularis flaps raised: Elevated up to the bony orbital rim 360°
5. Periosteum incised: Along the orbital margin 360°
6. Subperiosteal dissection: Freer periosteal elevator used to strip periosteum off the bony orbit from rim to orbital apex 360°
7. Supraorbital and zygomaticofacial neurovascular bundles identified and cauterised (bipolar)
8. Division at orbital apex: Optic nerve, superior orbital contents, and posterior tissues divided with curved scissors; massive sudden gentle pressure applied
9. Specimen removed en bloc
10. Haemostasis: Ice-cold wet gauze, bipolar cautery, Surgicel, bone wax
11. Frozen section of apical margin - to confirm clearance
12. Socket inspection: For any residual tumour
13. Closure: Lid flaps re-approximated over the socket
    • Orbicularis: 4-0 Vicryl
    • Skin: 6-0 Ethilon
14. Result: Concave skin-lined socket - ideal for prosthesis

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TYPE 2: Total Exenteration

• Incision made through full thickness of eyelids (skin, muscle, tarsus, conjunctiva)
• A skin incision is made around the orbital rim (at brow superiorly, cheek below, nasal bridge medially)
• Specimen includes: Both eyelids + all orbital contents including periorbita

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TYPE 3: Extended Exenteration

• All steps of total exenteration +
• Orbital wall resection: Lateral wall, roof (frontal bone), floor (orbital floor / maxilla), or medial wall (ethmoid) removed with oscillating saw / osteotomes
• Sinus clearance: Maxillary / ethmoid / frontal sinus clearance as needed
• Neurosurgical involvement: If intracranial extension
• Reconstruction typically requires free flap (radial forearm, anterolateral thigh)

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Socket Rehabilitation & Prosthesis

1. Adhesive prosthesis: Custom silicone eye socket prosthesis stuck with medical adhesive to surrounding skin
2. Spectacle-mounted prosthesis: Attached to glasses frame (Kanski's)
3. Osseointegrated implants (titanium fixtures): Drilled into orbital rim bones; magnets or clips fix the prosthesis → most stable, best cosmesis, no adhesive needed
   • Two-stage procedure: implants placed → 3-6 months → abutments + prosthesis
   • Kanski's: "Prostheses can be attached to the surrounding skin with adhesive, mounted on glasses, or secured with osseo-integrated magnets mounted on the orbital rim bones"

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Complications

Intraoperative Complications

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Early Postoperative Complications

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Late Postoperative Complications

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Comparison with Enucleation and Evisceration

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High-Yield Exam Points

1. Exenteration = most radical orbital surgery; removes globe + ALL orbital contents
2. Most common indication: Periorbital/eyelid malignancy (SCC, BCC, sebaceous carcinoma)
3. Most common eyelid tumour needing exenteration: Sebaceous gland carcinoma (due to pagetoid spread)
4. Lacrimal gland tumour needing exenteration: Adenoid cystic carcinoma (perineural spread, poor prognosis)
5. Non-malignant emergency indication: Mucormycosis (in diabetic / immunocompromised)
6. Lid-sparing (subtotal) = best cosmetic result; socket lined by preserved eyelid skin; prosthesis fits directly
7. Total exenteration socket options: Spontaneous granulation / STSG / Temporalis flap / Free flap
8. Gold standard flap for socket reconstruction: Temporalis muscle flap
9. Best long-term prosthesis fixation: Osseointegrated implants (titanium screws in orbital rim bones with magnets)
10. Most dangerous intraoperative complication: Massive haemorrhage (from ophthalmic artery at orbital apex)
11. CSF leak risk: Thin orbital roof → frontal lobe proximity → meningitis
12. Most common late complication: Sino-orbital fistula (especially medial wall / ethmoid breach)
13. Frozen section of orbital apex margin done to confirm complete tumour clearance
14. Kanski's prosthesis options: Adhesive / glasses-mounted / osseo-integrated magnets on orbital rim bones
15. Psychological counselling is mandatory pre-operatively - significant psychosocial disability

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Mnemonic: "SELAM PROBE" for Indications

• S - Sebaceous carcinoma (eyelid)
• E - Extended / invasive SCC / BCC
• L - Lacrimal gland adenoid cystic carcinoma
• A - Adenocarcinoma / other orbital malignancy
• M - Mucormycosis (non-malignant emergency)
• P - Primary orbital sarcomas (rhabdomyosarcoma etc.)
• R - Retinoblastoma (extraocular / neglected)
• O - Orbital invasion from sinuses
• B - Bulbar (uveal) melanoma with extrascleral extension
• E - Exenterated conjunctival melanoma

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