Endophthalmitis in Eyes Treated with the Port Delivery System with Ranibizumab: Summary of Cases during Clinical Trial Development.

PURPOSE: The Port Delivery System with ranibizumab (PDS) is approved in the United States for neovascular age-related macular degeneration. The United States Prescribing Information has a Boxed Warning for endophthalmitis and reports the incidence rate in patients developing endophthalmitis after receiving the PDS compared with monthly intravitreal ranibizumab. Endophthalmitis cases noted in the Boxed Warning, treatment outcomes, potential contributing factors, and potential mitigations are summarized. DESIGN: Retrospective review of endophthalmitis cases in PDS-treated patients in the phase II Ladder (NCT02510794) and phase III Archway (NCT03677934) and Portal (NCT03683251) trials. PARTICIPANTS: Endophthalmitis cases in the pooled all-PDS safety population (N = 555) including PDS patients in Ladder, Archway, or Portal. METHODS: Ladder patients received PDS (10, 40, or 100 mg/ml) with pro re nata refill-exchanges. Archway patients received PDS 100 mg/ml with fixed refill-exchanges every 24 weeks (PDS Q24W). Portal patients received PDS Q24W from day 1. MAIN OUTCOME MEASURES: Clinical features, management, and visual outcomes were summarized. Cases were summarized by date of PDS implant and/or refill, other prior invasive procedures/refills, and preceding/concurrent conjunctival complications. RESULTS: Twelve endophthalmitis events were reported in 11 patients (11/555 [2.0%]) through March 12, 2021. All were cultured (3 were culture positive) and treated with intravitreal antibiotics. Two cases (2/555 [0.4%]) occurred in the immediate postoperative period (days 5 and 6). Nine cases occurred later (day range: 57-853), including 4 before the first refill-exchange (day range: 57-161). Five patients received between 1 and 11 refill-exchanges before the event (onset: 6-168 days after last refill-exchange). Seven cases (7/11 [63.6%]) had preceding/concurrent conjunctival complications. At last follow-up, 7 patients recovered vision to study baseline levels or ≥20/40; 4 patients experienced vision loss of ≥15 ETDRS letters. CONCLUSIONS: Endophthalmitis is a serious complication that can endanger vision after any ocular procedure, including PDS implantation. Most, but not all, of this limited series of endophthalmitis cases were late onset, associated with conjunctival breach, and recovered vision with treatment. Meticulous attention to PDS surgical techniques with vigilant monitoring of conjunctiva during follow-up may minimize risk of endophthalmitis. Prompt treatment is critical for optimizing patient outcomes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

National survey of corneal cross-linking (CXL) practice patterns in the United Kingdom during 2019.

OBJECTIVE: To provide an insight into trends in corneal cross-linking (CXL) practice in the UK, including criteria for progression of corneal ectasia, identification of patients for CXL, the CXL procedure itself and post-operative management. METHODS: All ophthalmologist members of the UK Cross-linking (UK-CXL) Consortium were invited to complete an online survey about CXL practice for the year 2019. The data collected was anonymised by site and analysed with descriptive statistics. RESULTS: Responses were received from 16 individual CXL centres (16/38; 42% response rate) and the data represented ~2,000 CXL procedures performed in the UK in 2019. The commonest indication for CXL was progressive keratoconus. Between centres, there were variations in diagnostic evaluation, patient selection for CXL, the CXL procedure and the pre- and post-operative monitoring of patients. CONCLUSION: Consistent with the wide number of CXL treatment techniques described in the published literature world-wide, variations in the monitoring of corneal ectasia, indications for CXL, CXL practice and post-CXL follow-up were found to exist between UK-based CXL centres.

Effects of variation in depth and side cut angulations in LASIK and thin-flap LASIK using a femtosecond laser: a biomechanical study.

PURPOSE: To study the corneal biomechanical effects of varying LASIK flap depth and side cut angulations and evaluate the relative contribution of the lamellar and side cuts using a femtosecond laser and radial shearing speckle pattern interferometry (RSSPI). METHODS: Forty-two organ-cultured human corneas were divided into a control group and three investigative groups, each undergoing different incision types at both 90- and 160-µm depth using a femtosecond laser. In the first group, typical LASIK flaps were created; in the second group, only the bed was cut (delamination); and in the third group, side cuts alone were affected. Corneal strain was measured using RSSPI before and after treatment following an increase in hydrostatic pressure from 15.0 to 15.5 mmHg and again after 1 week of incubation in culture medium. RESULTS: The flap group demonstrated a weakening of strength related to the depth of cut, with strain increasing by 9% and 32% at 90 and 160 µm, respectively. Similar changes, 9% and 33%, were observed following execution of side cuts to the same depths. By contrast, strain increase following delamination showed no relationship with depth, increasing by 5% in both instances. When the side cut angle was made more acute, strain decreased with a 2% strain increase being measured after a 90-µm, 150° side cut was created. No significant changes occurred during the period of organ culture. CONCLUSIONS: Vertical side cuts through corneal lamellae rather than horizontal delamination incisions contribute to the loss of structural integrity during LASIK flap creation. Angulating side cuts such that the stromal diameter of the flap exceeds its epithelial diameter can decrease this effect.

Long-term topical steroid treatment after penetrating keratoplasty in patients with pseudophakic bullous keratopathy.

PURPOSE: To assess the use of long-term topical corticosteroid treatment in patients with pseudophakic bullous keratopathy (PBK) after penetrating keratoplasty (PK). DESIGN: Retrospective cohort study. PARTICIPANTS: This study considered patients with PBK undergoing an initial PK procedure for visual reasons in the United Kingdom between April 1999 and March 2004. There were 1274 initial PK procedures for PBK reported to United Kingdom Transplant in this period, of which 1184 (91%) were grafted for visual reasons. Of these 1184 grafts, follow-up was reported in 1033 instances (87%). METHODS: A Cox regression model was used to investigate the combined effects of all preoperative factors (recipient age, human leukocyte antigen [HLA] matching, trephine size, deep stromal vascularization, surgeon activity) on graft failure. The model was fitted using all preoperative factors first, and subsequently, factors associated with corticosteroid and other medications were included. MAIN OUTCOME MEASURES: Graft survival. RESULTS: Three-year survival of grafts for PBK was 65% (95% confidence interval [CI], 59%-70%). Topical corticosteroids were still being used beyond 18 months after surgery in 378 (37%) of the 1033 corneal grafts included in this study. The grafts of patients not currently receiving steroids were 1.5 times as likely to fail (hazard ratio [HR], 1.5; 95% CI, 1.0-2.2; P<0.03). Lack of HLA matching (P = 0.006), trephine size or=8.00 mm (P = 0.03), recipient age younger than 65 years (P = 0.003), and corneal vascularization (P = 0.04) all increased the risk of graft failure. CONCLUSIONS: The use of long-term postoperative corticosteroids improved graft survival after PK for PBK. Barring patient contraindications for long-term topical corticosteroid use, clinicians should consider maintaining patients with PBK on long-term postoperative corticosteroid maintenance.

Outcomes of same-sizing versus oversizing donor trephines in keratoconic patients undergoing first penetrating keratoplasty.

PURPOSE: To investigate whether use of same-size donor and recipient trephines reduced myopia after penetrating keratoplasty for keratoconus. DESIGN: Retrospective cohort study. PARTICIPANTS: Eight hundred seventy-eight first grafts for keratoconus were reported to UK Transplant between April 1999 and December 2003. There were 234 and 644 grafts in the same-size and oversize donor trephine groups, respectively. At 1 year, mean spherical equivalent (SE) data were available for 116 eyes (50%) and 295 eyes (46%) in the same-size and oversize groups. At 2 years, mean SE data were available for 64 eyes (27%) and 148 eyes (23%) in the same-size and oversize groups. METHODS: Logistic regression and univariate analysis of follow-up data submitted to UK Transplant. MAIN OUTCOME MEASURES: At 1 and 2 years postoperatively, mean SE, magnitude of the cylindrical component of the refraction, postoperative uncorrected visual acuity (VA), postoperative best-corrected VA, and postoperative complications were recorded. RESULTS: The mean SEs for the same-size and oversize donor trephine groups, respectively, were -1.45 diopters (D) and -1.41 D at 1 year (P = 0.6) and -1.74 D and -2.19 D at 2 years postoperatively (P = 0.3). Although there were no differences in graft survival between the groups at 1 and 2 years, there was a higher incidence of postoperative wound leaks in the same-size group (P = 0.03). CONCLUSION: Use of same-size donor and recipient trephines did not reduce myopia and was associated with an increased risk of postoperative complications.

Effects of ablation diameter on long-term refractive stability and corneal transparency after photorefractive keratectomy.

OBJECTIVE: To evaluate the effects of ablation diameter on long-term refractive stability and corneal transparency after photorefractive keratectomy (PRK). DESIGN: Long-term, prospective, follow-up study. PARTICIPANTS: One hundred twenty-three eyes treated between 1990 and 1993 at one institution as part of a number of ethical committee-approved clinical studies underwent long-term follow-up at 10 to 12 years after PRK. INTERVENTION: Photorefractive keratectomy was performed using the Summit Technology UV 200 and OmniMed Excimer lasers with either 4.0-mm (n = 36), 5.0-mm (n = 47), or 6.0-mm (n = 40) optical zones and either -3.0-diopters (D) or -6.0-D myopic spherical corrections, based on the original Munnerlyn algorithms. MAIN OUTCOME MEASURES: Refractive stability, refractive predictability, best spectacle-corrected visual acuity, and corneal haze. RESULTS: Refractive outcome at 1 and 10 to 12 years of follow-up was better with 6.0-mm treatments, especially for -6.0-D corrections (P>0.001). The early hyperopic shift was significantly reduced with 6.0-mm zones, with less regression between 1 and 6 months, compared with 5.0- and 4.00-mm PRK, especially for -6.0-D corrections (P<0.001). The postoperative refraction remained stable between 1 and 10 to 12 years in all groups. Objective measurements of haze were less with 6.0-mm compared with 4.0- and 5.0-mm treatments (P<0.001). Night vision problems were significantly less with 6.0-mm PRK (P<0.01). There was no evidence of progressive hyperopic shift, corneal ectasia, or late onset of corneal haze in any of the eyes during the follow-up period. CONCLUSIONS: Refractive stability was maintained between 1 year and 10 to 12 years after PRK with 4.0-, 5.0-, and 6.0-mm optical zones. A significant linear trend was observed in terms of refractive predictability, early hyperopic shift, regression, corneal transparency, and night haloes with better outcomes in PRK with a larger ablation zone. None of the eyes had sight-threatening complications such as ectasia or late-onset corneal haze during the follow-up.

5-year follow-up of LASIK for hyperopia.

PURPOSE: To assess the long-term efficacy and stability of LASIK for hyperopia (+0.75 to +7.00 diopters [D]). DESIGN: Retrospective follow-up study of a previous phase III multicenter clinical trial (unpublished data). PARTICIPANTS: Patients who had been treated for hyperopia (33 individuals, 47 eyes) attended follow-up 5 years after surgery. The preoperative mean spherical equivalent at the spectacle plane was +3.58 D (range, +0.75 to 7.00 D), and the attempted mean spherical correction at the corneal plane was +3.18 D (range, +1.00 to +6.00 D). INTERVENTION: Treatments were performed using a Moria LSK One microkeratome and a Summit Technology SVS Apex Plus excimer laser fitted with an Axicon. MAIN OUTCOME MEASURES: Manifest refraction, uncorrected visual acuity, best spectacle-corrected visual acuity, corneal transparency, complications, and patient satisfaction were recorded. RESULTS: At 5 years, for treatments between +1.00 to +3.00 D, 71.0% of eyes were within +/-1.00 D of the intended correction, and for treatments between +3.5 to +6.0 D, 37.5% of eyes were within +/-1.00 D of intended correction. From 12 to 54 months after surgery for all patients, there was a hyperopic shift of +0.53 D (range, -0.13 to +3.13 D), with 51.1% of eyes experiencing an increase of +0.50 D or more and 27.7% of eyes showing a hyperopic shift of more than +1.00 D. This hyperopic shift was +0.67 D (range, 0 to +1.125 D) for patients younger than 40 years of age and +0.44 D (range, -1.33 to +1.50 D) for patients between 43 and 55 years of age. CONCLUSIONS: LASIK was moderately effective for the correction of low degrees of hyperopia. However, there was regression throughout the 5-year follow-up that was greater than would be expected as a result of aging. Long-term stability of hyperopic LASIK refractive corrections, therefore, is uncertain.

Interferometric technique to measure biomechanical changes in the cornea induced by refractive surgery.

PURPOSE: To develop a technique to quantify biomechanical changes in the cornea after microkeratome incisions as would be performed in laser in situ keratomileusis. SETTING: St Thomas' Hospital, London, and the Wolfson School of Mechanical and Manufacturing Engineering, Loughborough University, Loughborough, United Kingdom. METHODS: Corneal displacements of whole sheep eyes were studied under hydrostatic loading using electronic speckle pattern interferometry before and after microkeratome incisions. RESULTS: After hydrostatic loading, there was a 20.7% increase in corneal displacement in corneas with microkeratome incisions compared to unoperated corneas; this was statistically significant (P=.0068, unpaired t test). CONCLUSIONS: Results show that in the formation of the microkeratome flap, collagen fibers are severed and minimal biomechanical loading is distributed through the flap. Corneal biomechanical integrity is compromised after microkeratome incisions.

Excimer laser photorefractive keratectomy for hyperopia: 7.5-year follow-up.

PURPOSE: To report the results of a long-term prospective study to evaluate refractive stability and safety of hyperopic photorefractive keratectomy (H-PRK). SETTING: Department of Ophthalmology, St. Thomas' Hospital, London, United Kingdom. METHODS: Twenty-one patients (49%) (40 eyes) of cohort of 43 patients who participated in 1 of the first clinical trials of H-PRK were assessed at a mean follow-up of 90.7 months (range 62 to 106 months). The H-PRK was performed using a Summit Technology Apex Plus Excimer laser (Summit Technology, Inc.). The mean preoperative spherical equivalent refraction (SEQ) was +4.70 diopters (D) (range +2.00 to +7.50 D). Patients were allocated to 1 of 4 treatment groups based on their preoperative refraction and received 1 of the following spherical corrections: +1.50 D, +3.00 D, +4.50 D, or +6.00 D. RESULTS: At 7.5 years, the refractive correction remained stable with a mean difference in SEQ between 1 year and 7.5 years of +0.28 D. The mean manifest SEQ was +0.83 D (range +5.00 to -3.00 D). Sixty-seven percent of eyes having corrections of +1.50 D and +3.00 D were within +/-1.00 D of the predicted correction. Predictability was poorer with +4.50 D and +6.00 D corrections, with 40% of eyes within +/-1.00 D of that expected. An improvement in uncorrected near acuity was achieved in 35 eyes (87.5%), and 35 eyes (87.5%) showed an improvement in uncorrected distance acuity from preoperative levels. Best spectacle-corrected visual acuity (BSCVA) was unchanged or improved from preoperative values in 25 eyes (62.5%). Three eyes (8%) lost 2 lines of Snellen BSCVA, which in 2 cases was attributable to cataract formation. A peripheral ring of haze, 6.5 mm in diameter, appeared in most eyes. Its intensity was greatest at 6 months and then diminished with time. In 10 eyes (25%), remnants of the haze ring were evident at 7.5 years and subepithelial iron rings, 6.5 mm in diameter were evident in 26 eyes (70%). No patient complained of night-vision problems and no eye developed ectasia. CONCLUSIONS: In H-PRK, refractive stability achieved at 1 year was maintained up to 7.5 years with no evidence of hyperopic shift, diurnal fluctuation, or late regression. Peripheral corneal haze decreased with time but was still evident in a number of eyes at the last follow-up visit.

A long-term study of photorefractive keratectomy; 12-year follow-up.

OBJECTIVE: To evaluate long-term refractive stability of excimer laser myopic photorefractive keratectomy (PRK). DESIGN: A long-term (12 years) prospective follow-up study. PARTICIPANTS: Sixty-eight patients (56.6%) of the original cohort of 120 who participated in the first United Kingdom excimer laser clinical trial underwent detailed clinical assessment at 12 years after myopic PRK. INTERVENTION: Myopic PRK was performed using the Summit Technology UV 200 excimer laser with a 4-mm ablation zone. Patients were allocated to 1 of 6 treatment groups based on their preoperative refraction. Each group received one of the following spherical corrections: -2, -3, -4, -5, -6, or -7 diopters (D). Patients in each group received an identical treatment, and therefore, emmetropia was not the primary aim. MAIN OUTCOME MEASURES: Refractive stability, refractive predictability, best spectacle-corrected visual acuity (BSCVA), and corneal haze. RESULTS: The postoperative refraction remained stable at 12 years, with no significant change in mean spherical equivalent refraction between 1, 6, and 12 years. Seventy-five percent of patients who underwent a -2-D correction and 65% of patients who received a -3-D correction were within 1 D of intended correction at 12 years. Fifty-seven percent of the -4-D group and 50% of the -5-D group were within 1 D, and this was further reduced to 25% and 22% in the -6-D and -7-D groups, respectively. Four percent had residual corneal haze, and 12% had persistent nighttime halos at 12 years. Dry eyes were encountered in 3% of patients, and none of the eyes developed corneal ectasia in the long term. CONCLUSIONS: In myopic PRK, refractive stability achieved at 1 year was maintained up to 12 years with no evidence of hyperopic shift, diurnal fluctuation, or late regression in the long term. Corneal haze decreased with time, with complete recovery of BSCVA. Night halos remained a significant problem in a subset of patients due to the small ablation zone size.

Three cases of intraocular foreign bodies as a result of walking or running along roadways.

PURPOSE: To report three cases of intraocular foreign bodies resulting from walking or running along roadways. DESIGN: Case reports. METHODS: Three separate incidents of walking or running along roadways with "traumatic events" resulting in intraocular foreign bodies. RESULTS: Each patient had pars plana vitrectomy with removal of intraocular foreign bodies. Chemical analysis was performed to give information on the potential origins of each foreign body. CONCLUSION: We hypothesize these intraocular foreign bodies were projected from the road surface with sufficient energy to penetrate the globe. Intraocular foreign bodies may result from simply walking or running along roadways.