Rapid spontaneous resolution of corneal hydrops in post-CXL keratitis

Abstract

An 11-year-old boy presented with right eye post-Corneal Collagen Cross-Linking (CXL) keratitis, which was complicated by acute corneal hydrops (CH). Keratitis was managed by topical antibiotics, and CH was managed conservatively. Cornea was monitored with serial anterior segment optical coherence tomography (ASOCT) scans. Spontaneous resolution of CH usually takes 8–12 weeks, but in this case it completely resolved in 3 weeks. Rapid resolution of CH after post-CXL keratitis could be attributed to a thinner cornea, increased interlamellar cohesive strength between collagen fibrils of corneal stroma coupled with normal functioning endothelial pump.

Background

Acute corneal hydrops (CH) is the development of corneal oedema due to a break in Descemet’s membrane (DM), which causes percolation of aqueous into corneal stroma. Acute CH occurs in 2.5%–3% of keratoconus (KC) cases and can occur in other corneal ectatic disorders like pellucid marginal degeneration and keratoglobus. CH after bacterial keratitis is a rare occurrence.

Case presentation

An 11-year-old boy presented with gradual, painless progressive diminution of vision in both eyes for 1 year associated with recurrent episodes of redness, itching and watering. His best-corrected visual acuity (BCVA) (with contact lens) was 20/30 and 20/40 in the right eye (RE) and left eye (LE), respectively.

Clinical examination revealed bilateral upper conjunctival papillae, inferior corneal thinning, Vogt’s striae and Fleischer’s ring. Scheimpflug corneal tomography (OCULUS Pentacam, Wetzlar, Germany) revealed inferior paracentral corneal steepening and central corneal thinning. K-max values were 59.7 D in RE and 69.7 D in LE. The thinnest corneal pachymetry was 431 µm in RE and 269 µm in LE. A diagnosis of both eyes vernal keratoconjunctivitis with KC Amsler Krumeich stage IV was made.

The child was advised against eye rubbing, and cold compresses were recommended. He was started on topical olopatadine 0.2% two times per day, topical cyclosporine 0.1% two times per day and carboxymethylcellulose 0.5% six times a day in both eyes. Subsequently, the child was planned for right eye iso-osmolar CXL to halt the progression of KC.

Three months later, he underwent RE epithelium-off accelerated CXL, with iso-osmolar riboflavin applied every 2 min for 20 min and UV treatment at 9 mW/cm² for 10 min. A bandage contact lens was placed at the end of the procedure, and topical moxifloxacin 0.5% and carboxymethyl cellulose 0.5% were started postoperatively.

On postoperative day 1, the child had a visual acuity (VA) of 20/200, with mild corneal haze, and was discharged. On postoperative day 3, he presented with acute onset redness, pain and diminution of vision in the RE with a VA of hand movements close to face (HMCF) with accurate projection of rays. His VA in LE remained unchanged. The bandage contact lens was removed and sent for bacterial and fungal culture and sensitivity. On examination of RE, there was diffuse perilimbal congestion, a central epithelial defect measuring 4 × 4 mm with surrounding infiltrates and 3+ anterior chamber cells. Ultrasound B scan for posterior segment evaluation revealed no abnormality. Hence, a diagnosis of RE post-CXL keratitis was made.

Corneal scraping showed gram-positive cocci. As per the institution protocol, the patient was started empirically on topical concentrated cefazolin 5% one hourly and concentrated tobramycin 1.3% one hourly till culture reports were available 48 hours later. Bacterial culture sensitivity of the scraping and bandage contact lens showed Staphylococcus aureus, susceptible to tobramycin and cefoxitin and resistant to ciprofloxacin and moxifloxacin. The fungal culture was sterile. We continued him on the same medications as there was a clinical improvement.

On postoperative day 8, although the ulcer size had reduced to 3 × 3 mm, an increase in corneal thickness with fluid clefts was noted in RE (figure 1A, B). There was no history of eye rubbing. Anterior segment optical coherence tomography (ASOCT) (Visante, Carl Zeiss Meditec, Dublin, California, USA) of RE showed superficial corneal infiltrates with a central corneal thickness (CCT) of 1140 µm and a rupture in DM (figure 2A). A diagnosis of spontaneous acute CH was made. Topical antibiotics were continued, and he was also started on topical prednisolone phosphate 1% four times a day, topical homatropine 2% four times a day, topical ointment sodium chloride 6% two times per day and topical timolol 0.5% two times per day in RE. Serial monitoring with daily ASOCT scans showed a decrease in corneal oedema and DM detachment. On postoperative day 10, RE CCT was 580 µm with 560 µm depth of DM detachment, and on postoperative day 14, RE CCT was 550 µm with 190 µm depth of DM detachment (figure 2B, C).

Figure 1.

Clinical photograph of post-CXL keratitis complicated with acute corneal hydrops. (A, B) Eighth postoperative day of CXL showing a 3 × 3 mm corneal ulcer with surrounding infiltrates and presence of intrastromal fluid clefts.

Figure 2.

Serial anterior segment optical coherence tomography (ASOCT) of post-CXL showing improvement in infiltrate, decrease in corneal oedema and Descemet’s membrane (DM) detachment. (A) Eighth postoperative day showing a hyperreflective area in the anterior half of the stroma along with corneal oedema. (B) Tenth postoperative day showing infiltrates with fluid cleft and DM detachment. (C) Fourteenth postoperative day showing a decrease in fluid cleft and DM detachment. (D) Twenty-eighth postoperative day showing resolution of DM detachment with corneal scarring.

Outcome and follow-up

On conservative management, CH showed rapid improvement. Keratitis also responded well to medical management. Corneal haze decreased, and pupillary details and lens status could be visualised. By postoperative day 21, RE VA improved to 20/400 with a CCT of 548 µm on ASOCT. By postoperative day 28, CH had completely resolved with a RE CCT of 450 µm (figure 2D); however, corneal infiltrates with a size of 1 mm × 1.5 mm, remained. The keratitis was resolved by postoperative day 34 with corneal scarring. The child had a RE BCVA of 20/240 on further follow-up and did not show a further progression of RE KC on up to 1 year follow-up.

Discussion

There is only one case report describing the occurrence of spontaneous CH in the setting of infectious keratitis, but the presence of pre-existing corneal ectatic disorder was not ruled out in that scenario.¹ As per the best of our knowledge, this is only the second reported case of a post-CXL keratitis eye complicated by acute CH.²

The natural history of bacterial keratitis involves stromal invasion followed by bacterial replication, the largest increase in the bacterial population occurring in the first 2 days of infection. The extensive inflammation causes a release of proteolytic enzymes, which cause liquefactive necrosis. Untreated, this progresses to DM rupture and frank corneal perforation.³ CXL causes the formation of stronger chemical bonds between collagen fibrils; the effect seen more in the anterior cornea. Further, crosslinked corneas of porcine eyes have demonstrated markedly increased resistance against collagen digesting proteolytic enzymes.⁴ We hypothesise that in this case of post-CXL keratitis, the proteolytic stromal degeneration occurred more in the posterior stroma, as compared with the anterior stroma, owing to the effects of crosslinking and initiation of topical antibiotic therapy. This, followed by DM detachment and tear, probably lead to CH, with post-CXL transient endothelial dysfunction being a potential contributing factor. Post-CXL endothelial dysfunction has been reported to cause corneal oedema within 24 hours of the procedure, which was not seen in the present case, and hence it could not have been a major risk factor for development of CH.⁵ When compared with an earlier reported case where the post-CXL keratitis resolved within a week, in this case, the keratitis resolved in 4 weeks. This might have prolonged the healing time of CH in this case. Interestingly, the CH resolved before complete healing of infective keratitis.

CH is diagnosed based on history and slit-lamp examination. Investigations like ultrasound biomicroscopy (UBM) and ASOCT help determine the size and extent of corneal oedema and DM tear and monitor the treatment outcome.⁶

Spontaneous resolution of acute CH takes over 2–4 months when managed conservatively. Methods like pneumatic descemetopexy have been shown to fasten the speed of recovery.^7–9 Two case reports where acute CH developed in a post-CXL cornea showed a complete resolution time of 7–8 days.^{2 10} The same was 21 days in the above described clinical case. Physiologically, during oedema, the anterior third of corneal stroma shows mild swelling due to lamellar interweaving in the collagen fibres. The posterior two-thirds of stroma with non-woven unidirectional fibrils can swell up to three times its average thickness.^{11 12} Crosslinking of corneal collagen creates additional bonds by photopolymerisation, which strengthens interlamellar cohesive strength. Crosslinked corneas have been demonstrated to have increased resistance to swelling.¹³ Stromal compaction and increased resistance to hydrostatic and osmotic fluid accumulation have been proposed mechanisms for the effect of CXL in reducing corneal oedema in pseudophakic bullous keratopathy (PBK) eyes. PBK eyes with thinner CCT at presentation have shown better outcomes after CXL, and a thin cornea in the above case could have been a contributing factor in the earlier resolution of the oedema.¹⁴ Also, in comparison with a mild reduction in corneal oedema seen in PBK eyes treated with CXL, a complete and rapid resolution of CH in the above case could be due to a normally functional endothelial pump.

Further studies would be required to evaluate this advantageous effect of CXL on the resolution of CH. Eyes with impending CH, especially in cases of thinner corneas, may be treated with limited/epithelium-on/contact lens assisted CXL to access the role of crosslinking in the prevention/resolution of CH. Also, the role of CXL in eyes with PBK may be evaluated earlier in the disease process when there is some limited normal endothelial function remaining, to assess if it prevents further progression of the disease. This might also serve as a stop-gap solution for PBK eyes requiring keratoplasty in regions with an imbalance in corneal tissue supply and demand.¹⁵

Patient’s perspective.

I was fine for a day after CXL procedure when suddenly I had this intense pain and my vision dropped. I am thankful to God that the entire episode is over.

Learning points.

• Corneal hydrops complicating a post-CXL keratitis is a rare occurrence, but it shows a faster resolution.

• Corneal hydrops occurring in an eye with pre-existing keratitis can be managed conservatively.

• Rapid resolution of corneal hydrops after post-CXL keratitis could be attributed to a thinner cornea, increased interlamellar cohesive strength between collagen fibrils of corneal stroma coupled with normal functioning endothelial pump.

Ethics statements

Patient consent for publication

Consent obtained from parent(s)/guardian(s).