Efficacy comparison of combining cross-linking and refractive laser ablation in progressive keratoconus: systematic review and meta-analysis.

OBJECTIVE: This study assessed the effect of combining corneal collagen cross-linking (CXL) with refractive laser ablation techniques for the treatment of keratoconus, a progressive corneal disorder. METHODS: We performed a systematic review and meta-analysis to assess the effect of combined CXL and refractive techniques. We included all published clinical trials or observational studies published by September 1, 2023. We calculated and compared the standardized mean difference (SMD) between CXL alone and CXL plus laser ablation for uncorrected distance visual acuity, best-corrected distance visual acuity, spherical equivalent manifest refraction, sphere and cylinder, flat keratometry (K1), steep keratometry (K2), and central corneal thickness. RESULTS: We identified 13 studies that fulfilled our inclusion and exclusion criteria. The average follow-up was 21.3 ± 11.8 months. The CXL plus laser ablation group showed improvement in uncorrected distance visual acuity logMAR (SMD, -0.35; 95% CI, -0.67 to -0.04; p = 0.029), best-corrected distance visual acuity logMAR (SMD, -0.17; 95% CI, -0.30 to -0.03; p = 0.014), spherical equivalent manifest refraction (SMD, -0.28; 95% CI, 0.06-0.50; p = 0.013), and change in maximal corneal curvature (Kmax; SMD, -0.41; 95% CI, -0.69 to -0.13; p = 0.004) compared with CXL alone. However, central corneal thickness decreased further among patients who underwent CXL plus laser ablation (SMD, -0.37; 95% CI, -0.66 to -0.07; p = 0.016). No effect was observed in terms of sphere (p = 0.878), cylinder (p = 0.859), K1 (p = 0.907), or K2 (p = 0.169). Ectasia was not observed as an adverse effect resulting from the additional corneal ablation performed during the CXL treatments. CONCLUSIONS: This study showed that combining refractive laser ablation techniques with standard or accelerated CXL treatment improved visual and refractive outcomes and anterior corneal curvature values.

Use of corneal cross-linking beyond keratoconus: a systemic literature review.

PURPOSE: The success of corneal collagen cross-linking in altering keratoconus' clinical course has driven a search for further uses of this procedure. This literature review aims to analyze the scientific evidence available for the benefit of cross-linking in the management of ophthalmic diseases other than progressive keratoconus or ectasia induced by corneal refractive procedures. METHODS: A systemic literature review. RESULTS: We reviewed 97 studies. We found that collagen cross-linking can limit the progression of several other corneal ectasias, thus reducing and limiting the need for keratoplasty. Collagen cross-linking also can reduce the refractive power of the cornea and can be considered for a moderate degree of bacterial keratitis or when the organism is unidentified, which is refractive to antibiotics alone. However, the comparative rarity of these procedures has limited the extent of evidence. In fungal, Acanthamoeba, and herpes virus keratitis, the evidence is inconclusive of the safety and efficacy of cross-linking. CONCLUSION: Current clinical data is limited, and laboratory data has not fully correlated with published clinical data.

Clinical study of laminar resorption: Part 2- outcomes, review and proposal for classification.

PURPOSE: To analyze and review the clinical features and main outcomes of laminar resorption from the UK osteo-odonto-keratoprosthesis (OOKP) cohort. METHODS: A retrospective review of case records was undertaken for patients who underwent keratoprostheses between 1996 and 2014 at the Sussex Eye Hospital, Brighton, UK. The main clinical outcomes of resorption, including its clinical signs, complications, treatments, and laminar survival, were evaluated. RESULTS: Sixty-four patients (25-females, 39-males) were included, and in total, 74 laminae (3-tibial, 11-allografts, 60-autografts) were implanted. The age of the patients ranged from 20 to 91 years. Focal laminar thinning was the first sign of detectable resorption in 50% of autografts and 27% of allografts. All the tibial grafts and 55% of allografts presented with complications of resorption like endophthalmitis and aqueous leakage as the first signs of resorption. The survival of first implanted autografts was 82.4%(±6.3%) at 18 years, which was enhanced to 91.5%(±5.0%) by prophylactic exchanges of critically resorbed laminae with new laminae. Visual acuity survival analysis did not reveal a statistically significant difference between grafts with and without resorption for all graft types (p = 0.825). Patients treated with Alendronic acid and acetazolamide demonstrated trends toward the slower progression of resorption, but this was not statistically significant. CONCLUSIONS: Focal laminar thinning was the common presenting feature of resorption in autografts. Timely replacement of the resorbed laminae with new laminae should be considered to avoid complications. Alendronic acid supplementation may be considered in high-risk cases of resorption to reduce further progression.

Clinical study of laminar resorption: Part 1 - Factors affecting laminar resorption.

PURPOSE: To analyse the factors affecting laminar resorption in the UK osteo-odonto-keratoprosthesis (OOKP) cohort and present a detailed review. METHODS: A retrospective review of the case records of the patients who underwent OOKP between 1996 and 2014 was performed at the Sussex Eye Hospital in Brighton, UK. RESULTS: Sixty-four patients (25 females and 39 males) were included, and 74 laminae were implanted consisting of 3 tibial grafts, 11 tooth allografts and 60 tooth autografts. In total, 69% (n = 51) showed resorption. Non-smokers had better oral health compared to smokers (71% vs 50%, respectively). Poor oral health was strongly associated with poor quality dentition and edentulism (p < 0.001). The laminar thickness and waiting for the time between stages 1 and 2 surgeries did not show significant influence on the onset and progression of resorption. From the Cox multivariate analysis for autografts, smoking, age and gender were not associated with a statistically significant difference in the rates of resorption. The maximum number of laminae with resorption belonged to Stevens-Johnson syndrome patients (n = 32 or 43%). CONCLUSIONS: Two-thirds of the cases of resorption were detected in the first three years of OOKP, and the maximum were noted in the first year of follow up (40%). The laminar thickness did not influence the post-operative onset and progression of resorption. The presence of resorption after stage 1 did not show a measurable effect on the onset and progression of post-stage 2 resorption.

Detection of laminar resorption in osteo-odonto-keratoprostheses.

PURPOSE: To compare the clinical examination and computerized tomography (CT) scanning methods for the detection of laminar resorption in eyes with osteo-odonto-keratoprosthesis (OOKP). METHODS: Patients who developed laminar resorption after OOKP surgery and had at least one CT scan of the lamina during the follow-up were included. Case records and CT images and reports were retrospectively reviewed. Each lamina of the eye was regarded as a case. The imaging and clinical data were collected in Microsoft Excel, and statistical analysis was performed on Stata-v14. The agreements and sensitivities of both the methods were compared. RESULTS: Forty patients out of 64 were found to have laminar resorption. A total of 48 laminae were studied, which had data on the presence or absence of resorption. The sensitivity and specificity of clinical detection of resorption were 87.5% (CI 68%-97%) and 37.5% (CI 8.5%-75.5%), respectively. Whereas, the sensitivity and specificity of CT scan were 81% (CI 61%-93%) and 50% (CI12%-88%), respectively. Both the methods have detected resorption in 21 out of 32 laminae having both the clinical and CT scan data. There is a fair agreement between the two techniques in the identification of thinned laminar sites. CONCLUSIONS: Clinical detection of laminar resorption in OOKP eyes is equally sensitive to the CT scanning. Resorption can be detected even in its early stages by clinical palpation in experienced hands. Frequent CT scanning is not indicated to detect laminar resorption. Both methods complement each other. Thinned laminar segments should be compared and correlated with both the methods for full evaluation of resorption.

Comparison of In Vivo Confocal Microscopy, PCR and Culture of Corneal Scrapes in the Diagnosis of Acanthamoeba Keratitis.

PURPOSE: Acanthamoeba keratitis (AK) is an uncommon but serious corneal infection, in which delayed diagnosis carries a poor prognosis. Conventional culture requires a long incubation period and has low sensitivity. Polymerase chain reaction (PCR) and in vivo confocal microscopy (IVCM) are available alternative diagnostic modalities that have increasing clinical utility. This study compares confocal microscopy, PCR, and corneal scrape culture in the early diagnosis of AK. METHODS: We reviewed the case notes of patients with a differential diagnosis of AK between June 2016 and February 2017 at the Bristol Eye Hospital, United Kingdom. Clinical features at presentation, and results of IVCM, PCR, and corneal scrape cultures were analyzed. RESULTS: A total of 25 case records were reviewed. AK was diagnosed in 14 patients (15 eyes). Based on the definition of "definite AK," the diagnostic sensitivities of IVCM, PCR, and corneal scrape cultures were 100% [95% confidence interval (CI), 63.1%-100%], 71.4% (95% CI, 41.9%-91.6%) and 33.3% (95% CI, 9.9%-65.1%), respectively. The 3 methods showed a specificity of 100% and a positive predictive value of 100%. Using a reference standard of only positive corneal cultures, IVCM, and PCR had a sensitivity of 100% (95% CI, 29.2%-100%) and 75% (95% CI, 19.4%-99.4%), respectively. CONCLUSIONS: All 3 diagnostic tests are highly specific, and a positive test result is highly predictive of disease presence. IVCM is both highly sensitive and specific when performed by an experienced operator. PCR is a useful adjunct in the diagnosis of AK because of its wider availability compared with IVCM, and it may be used in combination with IVCM for microbiologic confirmation.

Comparison of 640-Slice Multidetector Computed Tomography Versus 32-Slice MDCT for Imaging of the Osteo-odonto-keratoprosthesis Lamina.

PURPOSE: To investigate the efficacy of 640-slice multidetector computed tomography (MDCT) for detecting osteo-odonto laminar resorption in the osteo-odonto-keratoprosthesis (OOKP) compared with the current standard 32-slice MDCT. METHODS: Explanted OOKP laminae and bone-dentine fragments were scanned using 640-slice MDCT (Aquilion ONE; Toshiba) and 32-slice MDCT (LightSpeed Pro32; GE Healthcare). Pertinent comparisons including image quality, radiation dose, and scanning parameters were made. RESULTS: Benefits of 640-slice MDCT over 32-slice MDCT were shown. Key comparisons of 640-slice MDCT versus 32-slice MDCT included the following: percentage difference and correlation coefficient between radiological and anatomical measurements, 1.35% versus 3.67% and 0.9961 versus 0.9882, respectively; dose-length product, 63.50 versus 70.26; rotation time, 0.175 seconds versus 1.000 seconds; and detector coverage width, 16 cm versus 2 cm. CONCLUSIONS: Resorption of the osteo-odonto lamina after OOKP surgery can result in potentially sight-threatening complications, hence it warrants regular monitoring and timely intervention. MDCT remains the gold standard for radiological assessment of laminar resorption, which facilitates detection of subtle laminar changes earlier than the onset of clinical signs, thus indicating when preemptive measures can be taken. The 640-slice MDCT exhibits several advantages over traditional 32-slice MDCT. However, such benefits may not offset cost implications, except in rare cases, such as in young patients who might undergo years of radiation exposure.

Keratoprostheses for corneal blindness: a review of contemporary devices.

According to the World Health Organization, globally 4.9 million are blind due to corneal pathology. Corneal transplantation is successful and curative of the blindness for a majority of these cases. However, it is less successful in a number of diseases that produce corneal neovascularization, dry ocular surface and recurrent inflammation, or infections. A keratoprosthesis or KPro is the only alternative to restore vision when corneal graft is a doomed failure. Although a number of KPros have been proposed, only two devices, Boston type-1 KPro and osteo-odonto-KPro, have came to the fore. The former is totally synthetic and the latter is semi-biological in constitution. These two KPros have different surgical techniques and indications. Keratoprosthetic surgery is complex and should only be undertaken in specialized centers, where expertise, multidisciplinary teams, and resources are available. In this article, we briefly discuss some of the prominent historical KPros and contemporary devices.

A brief review of Boston type-1 and osteo-odonto keratoprostheses.

Globally there are ≈4.9 million bilaterally corneal blind and 23 million unilaterally corneal blind. Majority of this blindness exists in the developing countries, where resources for corneal banking and transplant surgery are less than adequate. Survival of corneal grafts gradually declines over the long term. Corneal transplantation has poor prognosis in vascularised corneal beds, ocular surface disease and viral keratitis. Keratoprosthesis (KPro) remains as a final option for end-stage ocular surface disease, multiple corneal transplant failures and high-risk corneal grafts. Boston type-1 KPro and osteo-odonto-keratoprosthesis are the two devices proven useful in recent years. Choice of a keratoprosthetic device is patient specific based on the underlying diagnosis, ocular morbidity and patient suitability. KPro surgery demands a high level of clinical and surgical expertise, lifelong commitment and extensive resources. Improvements in techniques and biomaterials may in the future provide retainable KPros that do not need regular follow-up of patients, have low complications but high retention rates and may be produced at a low cost on a mass scale to be available as 'off the shelf' devices. Because KPros have the potential to effectively address the burden of surgically treatable corneal blindness and may also eliminate the problems of corneal transplantation, more research is required to develop KPros as substitutes for corneal transplantation even in low-risk cases. In those countries where corneal blindness is a major liability, we need a two pronged approach: one to develop eye donation, eye banking and corneal transplantation and the second to establish centres for keratoprostheses, which are affordable and technically not challenging, in a population where default on follow-up visits are high. Until the latter is achieved, KPros should be viewed as a temporary means for visual restoration and be offered in national and supraregional specialised centres only.

Mitomycin-C for mucous membrane overgrowth in OOKP eyes.

PURPOSE: The aim of this study was to report the use of mitomycin-C (MMC) in the treatment of mucous membrane overgrowth in eyes with osteo-odonto-keratoprosthesis (OOKP). METHODS: Records of 4 cases with mucous membrane overgrowth after stage 2 OOKP surgery were reviewed. RESULTS: All the patients had undergone a mucous membrane trimming procedure followed by MMC application. None of the patients had any episode of recurrence of the mucous membrane overgrowth after a single application of MMC in the follow-up period that ranged from 1 to 11 years. CONCLUSIONS: MMC can successfully arrest mucous membrane overgrowth in OOKP-implanted eyes including refractory cases.

Suturing techniques and postoperative management in penetrating keratoplasty in the United Kingdom.

AIMS: To report on the suturing techniques and aspects of postoperative management in penetrating keratoplasty in the United Kingdom. METHODS: A postal questionnaire was sent to 137 ophthalmic consultants identified from a Royal College of Ophthalmology database as having a special interest in anterior segment surgery. The questionnaire surveyed surgeon preferences for surgical and suturing technique for penetrating keratoplasty surgery, and the postoperative care of corneal grafts. RESULTS: In all, 68% of questionnaires were completed and returned: 73% of respondents used a Flieringa ring or equivalent, 94% routinely used cardinal sutures, with 50.5% removing them at the end of the procedure. The most common suturing technique for routine penetrating keratoplasty was a single continuous suture (35%). In these cases, a 10/0 nylon suture was used by 89%. Sixty-six percent changed their technique in high-risk cases, 52% used a 3-1-1 knot, and 75% made a distinction between a reef and granny knot, with 76% using a reef. Thirty percent buried the knots within the donor material, and 29% within the host tissue. Twenty-five percent had no routine time for graft suture removal, but 41% removed them between 1 and 2 years post-surgery. After suture removal, 98% used steroids and 88% used topical antibiotics. Thirty-four percent stopped topical steroids before suture removal, with 38% stopping topical steroids more than 3 months prior to suture removal. CONCLUSION: This survey demonstrates that there is considerable variation in suturing techniques and postoperative care for penetrating keratoplasty. These significant variations in practice need to be considered when interpreting outcomes and research.

A 43-year-old woman on triptorelin presenting with pseudotumor cerebri: a case report.

INTRODUCTION: To the best of our knowledge, this is the first time triptorelin has been reported to cause benign intracranial hypertension. CASE PRESENTATION: A 43-year-old Caucasian woman who suffered from chronic menorrhagia was started on triptorelin, a gonadotrophin-releasing hormone analogue. Three days later, she developed gradually worsening headaches accompanied by bilateral visual disturbance. Examination revealed bilateral papilledema and enlarged blind spots on her visual fields. A diagnosis of benign intracranial hypertension was made and confirmed on magnetic resonance imaging. CONCLUSION: We recommend that patients at high risk (women who are overweight and of reproductive age) who are using any gonadotrophin-releasing hormone analogue (for example, triptorelin) should be periodically monitored for the possible development of benign intracranial hypertension.

Long-term ocular follow-up in a case with hereditary mucoepithelial dysplasia.

Hereditary mucoepithelial dysplasia is a rare desmosomal gap junction abnormality known to produce keratitis and cataracts in addition to multiple systemic problems. It generally carries a poor visual prognosis due to corneal scarring, amblyopia, and side effects of the treatment. The authors present a sporadic case of hereditary mucoepithelial dysplasia with an unusually good visual outcome and suggest that timely and appropriate intervention can improve the visual prognosis of this rare disorder.