Late-onset persistent corneal hydrops after crosslinking treated with 24% C3F8

Scott, Tabitha M. BKin, MD; Lee, Graham A. MD, MBBS, FRANZCO

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doi: 10.1097/j.jcro.0000000000000061
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A 31-year-old woman with keratoconus presented with right corneal hydrops. She had a history of right corneal crosslinking (CXL), epithelium-off using the Dresden protocol 9 years previously, with intermittent review for mini-scleral contact lens wear.1 The most recent keratometry reading in 2019 prior to the hydrops episode was 43.89 @ 147 and 43.72 @ 57. Her left eye had previous deep anterior lamellar keratoplasty and subsequent phacoemulsification with toric intraocular lens insertion. The patient was on no regular medications, had no significant family history, was a nonsmoker, and reported allergies to cats and dust mites. On examination, the corrected distance visual acuity was hand motion in the right eye and 20/40 in the left eye. The right cornea demonstrated inferior hydrops with gross thickening of the stroma.

Intracameral 14% C3F8 gas injection with 60% fill of the anterior chamber was performed in the clinic, and the patient postured supine for 1 hour. The patient was prescribed topical dexamethasone 4 times a day and atropine 1% daily. At 1 month, as there was no improvement of the hydrops, the intracameral injection of 14% C3F8 with 60% fill was repeated (Figure 1, A and B). Hypertonic saline 5% every 3 hours was commenced in addition to the other drops. The patient was reviewed monthly; however, by 6 months, there was no improvement. Throughout this review period, the patient requested conservative management, did not report discomfort with the hydrops, and could function with the vision in her left eye.

Figure 1.:
A: External photograph showing corneal hydrops and 14% C3F8 bubble at 1 month after injection. B: Pentacam image showing thickening of the cornea (pachymetry 1463 μm) and steep keratometry (77.9 @ 93.5, 89.6 d). C: External photograph showing 95% fill of the C3F8 bubble with intrastromal gas at the apex of the hydrops and posterior bowing of the iris. D: External photograph showing 60% fill of the C3F8 bubble with intrastromal gas at the apex of the hydrops and flattening of the iris after paracentesis to release of gas overfill.

At 6 months, intracameral 24% C3F8 with 65% fill was injected, and topical brimonidine 2 times day was commenced. The patient was reviewed daily, including intraocular pressure (IOP) measurement. On day 3, the patient reported eye pain, and the gas bubble was noted to be 95% intracameral volume, with an IOP of 19 mm Hg measured with rebound tonometry (Figure 1, C). The iris appeared concave on the anterior capsule. A paracentesis to release the bubble by 35% provided immediate relief of the pain (Figure 1, D). At 3-week review, the IOP was 6 mm Hg, the gas bubble at 15% intracameral volume and anterior subcapsular cataract noted (Figure 2, A). The Pentacam (Oculus Optikgeräte GmbH) showed flattening of the keratometry and resolution of the hydrops (Figure 2, BD).

Figure 2.:
A: External photograph showing resolution of the corneal hydrops, scarring over the apex of the hydrops, anterior subcapsular cataract, and intracameral 24% C3F8 bubble at 1 month after injection. B: Pentacam image showing thinning and flattening of the cornea (pachymetry 471 μm) and keratometry (47.8 @ 150.9, 47.8 d). C: External photograph showing the side profile of the cornea after resolution. D: External photograph showing the side profile of the corneal hydrops before treatment.


The presentation of corneal hydrops after CXL for keratoconus is a rare occurrence, with only 4 reported cases. However, it is likely that there are many cases that have occurred and have not been reported. The reported cases occurred in 1 female and 3 males, aged 15 to 26 years, from Lebanon, Brazil, Japan, and the United Kingdom.2–5 Three of the cases followed epi-off CXL and 1 after epithelium-on CXL.2–5 Each of the cases had a precipitating cause: allergic conjunctivitis, pregnancy, repeated eye rubbing, and microbial keratitis.2–5 Three of the 4 cases resolved within days to months, whereas the fourth, associated with allergic conjunctivitis, required keratoplasty.2–5 The management included the use of topical steroid, antibiotic, cycloplegic, and glaucoma drops, as well as hypertonic saline.2–5

In the current case, the corneal hydrops developed many years after epi-off CXL, despite stable keratometry readings over the 9 years. There was no obvious precipitating cause; however, the patient was known to rub her eyes in relation to her allergies. The corneal hydrops persisted for 6 months, despite 2 intracameral injections of 14% C3F8 gas. The patient found it difficult to posture in a flat supine position for prolonged periods; this might have resulted in suboptimal positioning for the inferiorly located Descemet tear. An advantage of using 24% C3F8 to obtain a 65% fill was that it was slightly expansile and, in this case, achieved a 95% fill after 2 days, whereby supine positioning was less critical. The experience using higher intracameral concentrations of C3F8 is limited; however, it has been reported that a 20% concentration in 4 experimental rabbit eyes resulted in reduced endothelial cell density, hexagonality, and increased corneal thickness.6 There have not been any human studies showing direct toxic effects to the endothelium, and reports of 100% C3F8 used for pneumatic vitreolysis have not shown apparent toxicity to the retina.7

Previous reports have suggested that C3F8 acts to accelerate resolution of the hydrops.8 Basu et al. found that patients with hydrops who were administered 0.1 mL nonexpansile 14% C3F8 improved corneal edema and symptoms compared with conservative treatment (78.7 ± 53.2 vs 117.9 ± 68.2 days P = .0001).8 Potential risks of intracameral gas include cataract formation from direct contact with inhibition of nutrient diffusion impeding proper lens metabolism.9 Gas-induced pupillary block glaucoma can be avoided with iridectomy.8 Compression sutures to approximate the torn edges of the Descemet membrane have been combined with gas; however, in our patient, she refused any operative procedure.10

Management with 24% C3F8 has not been trialed for hydrops treatment. The patients need to be followed daily for the first 3 days to check IOP rise and may benefit from topical or oral aqueous suppression agents. Although this patient did not have pain due to high IOP, the gas bubble causing posterior bowing and stretching of the iris was significant enough to warrant paracentesis, with immediate relief of the discomfort. There are no published model data on expansion of gases in the anterior chamber. However, there has been work done by Williamson et al. looking at the gas concentration required to achieve 100% fill of the vitreous cavity in the postoperative period.11 According to their data, 24% C3F8 would need to fill 63% of the vitreous cavity to achieve 100% gas fill if there is no leakage of the gas. Overfilling of an expansile gas potentially could result in ocular ischemia because of high IOPs, greater than 60 mm Hg.

In conclusion, this case indicates that corneal hydrops can occur many years after CXL. An expansile concentration of C3F8 gas was not used as first-line treatment, but only after repeated failure of conservative management options. It can be used with caution and careful follow-up.


  • Acute corneal hydrops is rare after crosslinking for keratoconus, reported to occur days to months after the procedure.
  • Corneal hydrops typically resolves within weeks to months with conservative treatment.
  • Nonexpansile concentration of C3F8 gas has been used to treat more recalcitrant corneal hydrops.


  • Acute hydrops can develop despite an apparently stable cornea status after crosslinking.
  • The duration of the hydrops can be prolonged, despite conservative treatment.
  • An expansile concentration of C3F8 gas at a set volume can be used to achieve a full anterior chamber with careful follow-up of IOP in the first 3 days.


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