Presentation

History of prior intraocular (cataract) surgery, presenting months to years later (average onset ~8 months to 7 years after surgery) with progressive blurred vision, glare, and haloes.
Pain, foreign-body sensation, and photophobia occur when epithelial bullae rupture and expose corneal nerve endings; this pain can be severe and recurrent.
Vision is typically worse on waking (reduced tear evaporation overnight allows more stromal fluid to accumulate) and may improve somewhat through the day.

Findings

★ Signature Finding

Painful epithelial bullae (fluid-filled blisters) overlying a diffusely oedematous, thickened cornea. Mechanism: progressive corneal endothelial cell loss/dysfunction below the density needed to maintain stromal deturgescence, leading first to stromal and then to epithelial oedema.

Diffuse stromal and microcystic epithelial oedema, Descemet folds; guttae may be present if underlying Fuchs dystrophy contributed.
Reduced endothelial cell density/abnormal morphology on specular microscopy when imaging is possible.
May have a coexisting anterior chamber IOL or vitreous in the anterior chamber from prior complicated surgery, contributing to ongoing endothelial trauma.

Etiology & Mechanism

Pre-operative factors: a low baseline endothelial cell count (age-related attrition, prior Fuchs dystrophy) increases susceptibility.
Intra-operative factors: direct mechanical trauma from instruments or the IOL, excessive phacoemulsification energy/time, toxic anterior segment syndrome (TASS) from irrigating-solution toxicity, and posterior capsular rupture with vitreous prolapse.
Post-operative factors: chronic inflammation, glaucoma, and ongoing IOL-endothelium touch (particularly with anterior chamber IOLs) perpetuate cell loss.
The adult corneal endothelium has essentially no regenerative capacity (the cells are postmitotic), so loss is cumulative and irreversible once density falls below the threshold needed to maintain corneal clarity.

Red Flags — Do Not Miss

Critical — Do Not Miss

Pain with a red eye and decreased vision after cataract surgery — first exclude concurrent infectious endophthalmitis or uveitis before attributing the picture entirely to bullous keratopathy.
Rapidly progressive corneal decompensation in the immediate post-operative period (within 12–48 hours) — consider toxic anterior segment syndrome (TASS), a distinct acute entity requiring different recognition and management from chronic, late-onset PBK.
Elevated IOP in the setting of bullous keratopathy — secondary glaucoma is a frequent co-morbidity that must be identified and controlled.

Investigations

Slit-lamp exam to characterise the extent of stromal/epithelial oedema and bullae, and to assess IOL position, presence of vitreous, and inflammation in the anterior chamber.
Pachymetry to quantify corneal thickness/oedema and monitor progression.
Specular microscopy for endothelial cell density/morphology where corneal clarity allows imaging.
Anterior segment OCT to characterise corneal architecture and bullae and assist surgical planning when the view is limited.
Gonioscopy and IOP assessment for coexisting/secondary glaucoma.

Management

Address any coexisting or contributing IOP elevation or inflammation medically first.
If an anterior chamber IOL or vitreous strands are contributing to ongoing endothelial trauma, surgical planning should address IOL exchange/removal or anterior vitrectomy as part of definitive management.
Conservative measures for milder or early disease, or while awaiting/planning definitive surgery.

Treatment

Conservative/symptomatic: hypertonic saline drops or ointment (commonly 5% sodium chloride, e.g., Muro 128) to osmotically dehydrate the corneal stroma; a bandage soft contact lens to reduce pain from ruptured bullae.
Definitive treatment: corneal transplantation. Endothelial keratoplasty — DSEK/DSAEK or DMEK — has largely replaced penetrating keratoplasty (PK) as the treatment of choice, offering faster visual recovery, less induced astigmatism, and a closed-globe approach.
PK or a combined approach remains necessary in complex cases (e.g., significant AC IOL complications, microcornea, or when EK is not technically feasible).
Emerging option: Rho-kinase (ROCK) inhibitors have shown promise in early clinical studies for promoting endothelial cell proliferation/migration, but this remains evolving and is not yet standard of care.

Follow-up

Regular monitoring of corneal status, IOP, and pain control while planning definitive surgical treatment.
Post-keratoplasty: close early follow-up for graft attachment — particularly important after DMEK/DSEK, given detachment risk, which may require re-bubbling with intracameral air or gas.
Rejection surveillance and long-term monitoring of graft endothelial cell density, since gradual attrition continues even after a successful graft.

Clinical Pearl

💡 Clinical Pearl

Because the adult corneal endothelium cannot regenerate, pseudophakic bullous keratopathy is a race against a fixed, non-renewable cell pool — recognising and minimising intra-operative endothelial risk factors (excess phaco energy, TASS, IOL-endothelium touch) is the most effective way to prevent this painful, vision-threatening late complication.

Differential Diagnoses

Condition	Key Distinguishing Point
Fuchs endothelial corneal dystrophy	Bilateral, guttae visible even without prior surgery, family history; can also coexist with and compound PBK.
Herpetic (HSV/VZV) endothelial/disciform keratitis	Typically unilateral oedema with KPs and decreased corneal sensation; history of prior herpetic eye disease, no necessary surgical history.
Toxic anterior segment syndrome (TASS)	Acute, within 12–48 hours of cataract surgery (far faster onset than typical PBK), diffuse limbus-to-limbus oedema, usually without significant pain or hypopyon.
Interface fluid syndrome / graft rejection	History of prior keratoplasty; specific slit-lamp findings of graft-host interface fluid or an endothelial rejection (Khodadoust) line.
Congenital hereditary endothelial dystrophy	Relevant only in the paediatric differential of corneal oedema (present from infancy), not in adult acquired PBK.

Pupilla

Aphakic / Pseudophakic Bullous Keratopathy