Late-Onset Chronic Corneal Fistula Following Phototherapeutic Keratectomy: A Case Report and Importance of Early Detection.

BACKGROUND We report a case of late-onset chronic fistula in a decompensated cornea after multiple ocular surgeries and a recent phototherapeutic keratectomy (PTK). CASE REPORT A 73-year-old woman presented to our service with a past ocular history of bilateral chronic angle closure glaucoma and pseudophakic bullous keratopathy in the left eye. Given a history of long-term uncontrolled glaucoma with advanced disc cupping and poor visual potential, the patient underwent multiple palliative procedures, including, most recently, a PTK. Few years later she presented with a spontaneous late onset of slowly appearing corneal leak on fluorescein staining upon routine clinical examination. Corrected distance visual acuity was hand motion and intraocular pressure (IOP) was 40 mmHg in the affected eye. Serial anterior segment optical coherence tomography (AS-OCT) sections were obtained, which aided in understanding the current presentation and revealed distinctive multilayer corneal changes during the healing process. The patient was successfully managed with cyanoacrylate corneal gluing and ocular hypotensive medications, which halted the corneal leak. CONCLUSIONS We report a case of a rare finding of corneal fistula in an eye with multiple previous ocular surgeries, and provide an explanation of the possible etiopathogenesis. We also highlight the pivotal role of AS-OCT for evaluating such cases and stress the importance of early detection of similar subtle leaks in the setting of a formed anterior chamber, which can often be missed, carrying a risk of infection.

Topical calcitriol application promotes diabetic corneal wound healing and reinnervation through inhibiting NLRP3 inflammasome activation.

Vitamin D (VD) deficiency delays corneal wound healing in those with diabetes, which cannot be rescued with supplemental diet. Here, we employed topical calcitriol application to evaluate its efficiency in corneal wound healing and reinnervation in diabetic mice. Type 1 diabetic mice were topically administrated calcitriol, or subconjunctivally injected with NLRP3 antagonist MCC950 or IL-1ß blocking antibody after epithelial debridement. Serum VD levels, corneal epithelial defect, corneal sensation and nerve density, NLRP3 inflammasome activation, neutrophil infiltration, macrophage phenotypes, and gene expressions were examined. Compared with those of normal mice, diabetic mice showed reduced serum VD levels. Topical calcitriol application promoted corneal wound healing and nerve regeneration, as well as sensation recovery in diabetic mice. Moreover, calcitriol ameliorated neutrophil infiltration and promoted the M1-to-M2 macrophage transition, accompanied by suppressed overactivation of the NLRP3 inflammasome. Treatment with NLRP3 antagonist or IL-1ß blockage demonstrated similar improvements as those of topical calcitriol application. Additionally, calcitriol administration upregulated desmosomal and hemidesmosomal gene expression in the diabetic cornea. In conclusion, topical calcitriol application promotes corneal wound healing and reinnervation during diabetes, which may be related to the suppression of the overactivation of NLRP3 inflammasome.

Progesterone Application to the Rat Forehead Produces Corneal Antinociception.

Purpose: Ocular pain and discomfort are the most defining symptoms of dry eye disease. We determined the ability of topical progesterone to affect corneal sensitivity and brainstem processing of nociceptive inputs. Methods: Progesterone or vehicle gel was applied to the shaved forehead in male Sprague Dawley rats. As a site control, gel also was applied to the cheek on the side contralateral to corneal stimulation. Corneal mechanical thresholds were determined using the Cochet-Bonnet esthesiometer in intact and lacrimal gland excision-induced dry eye animals. Eye wipe behaviors in response to hypertonic saline and capsaicin were examined, and corneal mustard oil-induced c-Fos immunohistochemistry was quantified in the brainstem spinal trigeminal nucleus. Results: Progesterone gel application to the forehead, but not the contralateral cheek, increased corneal mechanical thresholds in intact and lacrimal gland excision animals beginning <30 minutes after treatment. Subcutaneous injection of the local anesthetic bupivacaine into the forehead region before application of progesterone prevented the increase in corneal mechanical thresholds. Furthermore, progesterone decreased capsaicin-evoked eye wipe behavior in intact animals and hypertonic saline evoked eye wipe behavior in dry eye animals. The number of Fos-positive neurons located in the caudal region of the spinal trigeminal nucleus after corneal mustard oil application was reduced in progesterone-treated animals. Conclusions: Results from this study indicate that progesterone, when applied to the forehead, produces analgesia as indicated by increased corneal mechanical thresholds and decreased nociceptive responses to hypertonic saline and capsaicin.

Optical coherence tomography of the Kayser-Fleischer ring: an ancillary diagnostic tool for Wilson's disease in children.

This report presents anterior segment optical coherence tomography (AS-OCT) images of Kayser-Fleischer ring (KFR) in a child. The AS-OCT images highlight differential reflectivity of the KFR depending on amount of copper deposited in cornea, thus supporting the role of AS-OCT as a follow-up tool. Utility of AS-OCT for diagnosing and documenting the KFR in children otherwise uncooperative for detailed slit lamp examination is discussed.

Plasmapheresis, Intravenous Immunoglobulins, and Autologous Serum Eyedrops in the Acute Eye Complications of Toxic Epidermal Necrolysis.

PURPOSE: Toxic epidermal necrolysis (TEN) is a rare, life-threatening, drug-induced, mucocutaneous disease, which can severely affect the ocular surface. The purpose of this study was to investigate the efficacy of plasmapheresis, human IV immunoglobulins (IVIg), and autologous serum (AS) eyedrops in the treatment of the severe acute ocular complications of TEN. METHODS: A retrospective chart review of all patients admitted to the Burn Unit, Azienda Ospedaliero-Universitaria-Sassari, Sassari, Italy, from 2009 to 2015, identified 9 patients (2 men, 7 women; mean age 63.8 ± 24.7 years) with TEN. Bilateral, acute ocular surface complications were observed in 7 (78%) patients; 3 showed catarrhal conjunctivitis, whereas 4 had severe pseudomembranous conjunctivitis and corneal ulcers. RESULTS: All patients with TEN were immediately treated with plasmapheresis and human IVIg, which produced a marked improvement in the patients' general condition. In the 3 with catarrhal conjunctivitis, preservative-free artificial tears and topical antibiotics were beneficial. In the 4 with severe pseudomembranous conjunctivitis and corneal ulcers, treatment with AS eyedrops resulted in corneal and conjunctival epithelium healing over 3-6 weeks. After a minimum follow-up of at least 12 months, there were minimal/mild residual signs and symptoms of dry eye. CONCLUSIONS: Plasmapheresis and IVIg may be life-saving and contribute to reduce ocular surface inflammation in TEN. Autologous serum eyedrops, prepared after plasmapheresis completion and IVIg infusion, may be helpful in the management of the severe acute ocular complications of TEN.

Corneal Endothelial Alterations in Chronic Renal Failure.

PURPOSE: To evaluate the corneal endothelial changes in patients with chronic renal failure. METHODS: A total of 128 corneas of 128 subjects were studied, and 3 groups were formed. The first, the dialyzed group, composed of 32 corneas of 32 patients; the second, the nondialyzed group, composed of 34 corneas of 34 patients; and the third, the age-matched control group, composed of 64 corneas of 64 healthy subjects were examined by a specular microscope and the endothelial parameters were compared. The dialyzed group (enhanced level of toxins in the blood) was further analyzed to assess the influence of blood urea, serum creatinine, serum calcium, and serum phosphorus including the duration of dialysis on corneal endothelium. RESULTS: On comparing the 3 groups using analysis of variance and posthoc tests, a significant difference was found in the central corneal thickness (CCT) and endothelial cell density (CD) between the control (CCT: 506 ± 29 µm, CD: 2760 ± 304 cells/mm) and dialyzed groups (CCT: 549 ± 30 µm, CD: 2337 ± 324 cells/mm) [P < 0.001 (CCT); P < 0.001 (CD)]; control and nondialyzed groups (CCT: 524 ± 27 µm, CD: 2574 ± 260 cells/mm) [P = 0.023 (CCT); P = 0.016 (CD)]; and dialyzed and nondialyzed groups [P = 0.002 (CCT); P = 0.007 (CD)]. Using the linear generalized model, a significant correlation was found between the endothelial parameters and blood urea only [P = 0.006 (CCT), 0.002 (coefficient of variation), 0.022 (CD), and 0.026 (percentage of hexagonality)], although the correlation was poorly positive for CCT but poorly negative for the remaining endothelial parameters. CONCLUSIONS: Corneal endothelial alteration is present in patients with chronic renal failure, more marked in patients undergoing hemodialysis and with raised blood urea level.

Electrical Stimulation of the Trigeminal Ganglion and Intrathecal Drug Delivery Systems for the Management of Corneal Neuropathic Pain.

PURPOSE: This case study reports on 2 novel neuromodulatory approaches in the management of a particularly recalcitrant case of corneal neuropathic pain. METHODS: Report of a case RESULTS: : A 32-year-old woman presented with intractable bilateral dry eye-like symptoms and corneal neuropathic pain after undergoing laser in situ keratomileusis surgery. Extensive ocular and systemic therapies were unsuccessful. Implantation of an electrode for the electrical stimulation of the trigeminal ganglion resulted in complete resolution of symptoms, but pain recurred after lead migration. Implantation of an intrathecal infusion system for fentanyl and bupivacaine delivery at the C1-C2 level resulted in control of her symptoms with excellent pain relief for more than 1 year. CONCLUSIONS: Electrical stimulation of the trigeminal ganglion and a high cervical intrathecal pain pump can be used in the management of corneal neuropathic pain unresponsive to ocular and systemic approaches.

Collagen cross-linking in recalcitrant corneal ulcers: A case series.

INTRODUCTION: Corneal ulcer is a leading cause of blindness worldwide. Many of these patients don't respond to conventional treatment with topical agents. Collagen cross-linking (CXL) has been suggested to avoid complications requiring emergency keratoplasty. SUBJECTS AND METHODS: Six eyes with presumed bacterial keratitis not responding to conventional treatment underwent CXL with ultraviolet A rays and transepithelial riboflavin. Patients with Descematocele and perforated ulcers were excluded. Preoperatively and postoperatively slit lamp examination of cornea and visual acuity recording was done. Postoperative outcome included subjective symptoms like relief in pain, photophobia, lacrimation and objective signs like improvement in epithelisation, corneal scarring with vascularisation. RESULTS: Four of the six eyes healed completely with scarring at 2 months follow-up. One of the patients developed Descematocele on 12 days which perforated later. Other patient developed Descematocele on 20 days post CXL. Of the subjective symptoms, pain and epiphora improved in all the patients except one. Photophobia improved only a week after CXL in four out of six patients. Epithelial defect completely healed over time in four out of six cases. All the cases who responded to treatment developed superficial and deep vascularisation of the cornea. Decrease in corneal edema and scarring was noted in four out of the six cases. CONCLUSION: The collagen cross-linking has a beneficial role as an adjuvant to medical therapy in recalcitrant bacterial keratitis. It helps in relief of pain and healing of ulcer. Larger randomized control trails with longer follow-up are required to come to a definite conclusion.

Usefulness of flat detector CT (FD-CT) with biplane fluoroscopy for complication avoidance during radiofrequency thermal rhizotomy for trigeminal neuralgia.

INTRODUCTION: Trigeminal neuralgia (TN) is characterized by episodes of shooting pain in the areas innervated by one or more divisions of the trigeminal nerve. The initial treatment of TN is with drugs but the increased frequency and intensity of the neuralgic episodes often force the patient to seek alternative therapies. Microvascular decompression (MVD) and radiofrequency thermal lesioning of trigeminal rootlets (RFTR) offer close to the best results for TN. MVD has the disadvantage of being an open surgical procedure with its attendant risks and longer hospital stay, whereas RFTR is a short, 'day-care' procedure. However this latter procedure involves positioning of the RF needle in the area behind the trigeminal ganglion through the foramen ovale, which can pose significant challenges. OBJECTIVE: To use the fluoroscopic support of a biplane catheter laboratory to access the foramen, and flat detector CT to confirm the location of the tip of the RF needle in the optimal position. METHODS: Fifty-three patients with TN underwent RFTR under local anesthesia with conscious sedation. RESULTS: All patients reported pain relief with hypesthesia over the offending trigeminal division. In seven patients the needle tip required repositioning according to the CT images. Two patients each had loss of corneal reflex and abducens nerve palsy after the procedure. No other complications were seen. CONCLUSIONS: The superior view in two planes coupled with the anatomical confirmation of the position of the needle tip in the Meckel's cave during the rhizotomy reduces the need for multiple passages of the needle to access the foramen ovale and achieves accurate needle tip positioning. The technique increases the safety and precision of such treatments and helps to manage potential complications.

Hypercholesterolemia-induced ocular disorder: Ameliorating role of phytotherapy.

The ocular region is a complex structure that allows conscious light perception and vision. It is of ecto-mesodermal origin. Cholesterol and polyunsaturated fatty acids are involved in retinal cell function; however, hypercholesterolemia and diabetes impair its function. Retinal damage, neovascularization, and cataracts are the main complications of cholesterol overload. Dietary supplementation of selected plant products can lead to the scavenging of free reactive oxygen species, thereby protecting the ocular regions from the damage of hypercholesterolemia. This review illustrates the dramatic effects of increased cholesterol levels on the ocular regions. The effect of phytotherapy is discussed in relation to the different regions of the eye, including the retina, cornea, and lens.

Monitor corneal epithelial healing under bandage contact lens using ultrahigh-resolution optical coherence tomography after pterygium surgery.

OBJECTIVE: To monitor corneal epithelial healing under bandage contact lens (BCL) using ultrahigh-resolution optical coherence tomography (UHR-OCT) after pterygium surgery. METHODS: Thirty-nine eyes of 39 patients undergoing pterygium excision and conjunctival autografting were randomly allocated into 2 groups: 20 eyes were covered with silicone hydrogel BCLs at the end of surgery and 19 eyes served as a control. Ultrahigh-resolution optical coherence tomography scans of the cornea were performed sequentially at 1, 2, and 3 days, and then every other day until the end of re-epithelialization after surgery. Complete epithelial healing was verified with fluorescein staining examination after removal of BCLs. Postsurgery pain was evaluated using the visual analog scale. RESULTS: All BCLs were successfully fit without any contact lens-related complications. Ultrahigh-resolution optical coherence images clearly revealed the architectural features of postoperative cornea with BCL in situ and showed epithelial healing process. Ultrahigh-resolution optical coherence tomography imaging agreed with the fluorescein staining examinations in detecting corneal epithelial defect. Based on the assessment by UHR-OCT, the average time course of re-epithelialization in the BCL group was 3.9±1.2 days, whereas in the control group, it was 5.7±1.8 days (P=0.001). Visual analog scale scoring showed lower pain levels in the BCL group comparing with the control group at each point of time (all P<0.05). CONCLUSIONS: Ultrahigh-resolution optical coherence tomography is an excellent tool in monitoring corneal epithelial healing under BCLs and determining the appropriate time for lens removal. Silicone hydrogel BCL is recommended as an adjuvant therapy after pterygium surgery for its efficacy in improving re-epithelialization and postoperative comfort.

Corneal epitheliopathy in congenital methemoglobinemia.

PURPOSE: The aim of this study was to describe a previously unreported characteristic corneal epitheliopathy in congenital methemoglobinemia (type 1). METHODS: This was an observational case series of ocular findings in congenital methemoglobinemia. RESULTS: Siblings of 2 different affected families (age range, 12-14 years; 3 girls, 1 boy) affected with congenital methemoglobinemia had similar ocular complaints and clinical presentation. All of them had recurrent episodes of irritation and tearing in both eyes. Slit lamp biomicroscopy examination in all of them revealed the presence of dark colored corkscrew conjunctival vessels (prominently seen on the tarsal and forniceal region) and grayish-white raised corneal epithelial lesions. Diagnostic corneal scrapings in 2 of the patients showed the presence of epithelial cells with nonspecific inflammatory cells, and the results were negative for microbes. None of the patients had any abnormality in the lid adnexa, blink response, corneal sensation, or in the tear film. The corneal lesions resolved in 2 to 3 weeks time while on supportive therapy alone and on vitamin C supplements. CONCLUSIONS: Dark colored conjunctival vessels and recurrent corneal epitheliopathy causing irritation and tearing may be ocular features associated with congenital methemoglobinemia. It is pertinent for ophthalmologists, hematologists, and pediatricians to be aware of this association.

Dietary α-lipoic acid prevents UVB-induced corneal and conjunctival degeneration through multiple effects.

PURPOSE: This study investigated the effects of dietary α-lipoic acid (α-LA) against ultraviolet B (UVB)-induced corneal and conjunctival degeneration in a mouse model. METHODS: Female CBA mice were randomly divided into five study groups, including blank control, UVB without α-LA, and UVB with dietary α-LA at 1, 10, and 100 mg/kg body weight. Following UVB exposure, corneal surfaces were assessed along with immunohistochemistry for nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), malondialdehyde (MDA) accumulation, and P63⁺ basal cell distribution. Matrix metalloproteinase (MMP)-2 and MMP-9 activities were determined by gelatin zymography. ELISA assay was performed to confirm the findings of immunohistochemistry for NF-κB, COX-2, and MDA, along with the levels of TNF-α and IL-6. Tear production and goblet cell density were determined after tear strip assay and periodic acid Schiff staining, respectively. RESULTS: The results showed that UVB irradiation caused corneal surface damage, polymorphonuclear leukocyte infiltration, and loss of P63⁺ basal cells. Dietary α-LA ameliorated the UVB-induced corneal damage while simultaneously reducing MDA accumulation and maintaining P63⁺ basal cell survival. NF-κB-p65, COX-2, TNF-α, IL-6, and MMP-9 activity were all reduced by dietary α-LA. In addition, α-LA helped to reverse aqueous tear reduction, conjunctival squamous epithelium metaplasia, and goblet cell loss after UVB exposure. CONCLUSIONS: Dietary α-LA can prevent UVB-induced corneal damage and can be used as a prophylactic agent prior to excessive UVB exposure.

Minimising corneal scarring from the use of harmful traditional eye remedies in developing countries.

Corneal scarring is the fourth largest cause of blindness globally, and a much more prominent factor in developing countries. Blindness from corneal scarring is largely a preventable phenomenon, and is capable of causing significant morbidity that can last for a lifetime. A significant proportion of these cases are caused by the use of harmful traditional eye medicines/remedies, and are used and prescribed by friends, relatives and traditional healers, with widespread use especially in developing countries. Use of traditional remedies can also cause harm indirectly by causing delays before seeking medical treatment. Reducing corneal scarring from the use of harmful traditional medicine is through a combination of approaches with the key strategies being community diagnosis, education, participation, and intervention, with provision of basic eye care integrated into the primary health care of the community. Collaboration with traditional healers in the community is also another approach that has been found to be useful.

Post-LASIK keratectasia triggered by eye rubbing and treated with topography-guided ablation and collagen cross-linking--a case report.

PURPOSE: To report a case of unilateral post-laser-assisted in situ keratomileusis (LASIK) keratectasia in a 35-year-old woman who had no known predisposing risk factors but who rubbed her affected eye frequently and vigorously in response to allergic conjunctivitis. METHODS: Case report with relevant literature review. RESULTS: A 35-year-old woman, with a cumulative risk scale score of 0 (according to the Randleman criteria), who underwent bilateral LASIK developed unilateral post-LASIK keratectasia 32 months later. She presented with a history of vigorous eye rubbing of the affected eye since about a year after allergic conjunctivitis. The fellow eye, which was not rubbed, remained normal. She complained of glare, halos, and ghost images in her affected eye. She underwent transepithelial topography-guided customized ablation with simultaneous UV-A corneal collagen cross-linking, after which she improved symptomatically and topographically. CONCLUSIONS: Eye rubbing could contribute to the development of keratectasia, even in an eye that has no subclinical features of the disease. When detected early, a simultaneous combined topography-guided customized ablation treatment and collagen cross-linking is effective in improving the irregular corneal contour and restoring biomechanical stability.

The role of heat in rubbing and massage-related corneal deformation.

PURPOSE: To examine the role of elevated corneal temperature in the development of rubbing/massage-related corneal deformation and the possibility that warm compresses in the management of meibomian gland dysfunction or chalazion could contribute to such adverse responses. METHODS: With reference to reports of corneal deformation associated with meibomian gland dysfunction, chalazion, dacryocystoceles and post-trabeculectomy, the mechanisms for increased corneal temperature due to ocular massage, especially when combined with warm compresses are examined. RESULTS: Several mechanisms for rubbing/massage to elevate corneal temperature have been described, apart from the application of warm compresses or other forms of heat. CONCLUSIONS: Raised corneal temperature helps to explain corneal deformation which develops in association with rubbing or massage in conditions such as keratoconus, chalazion, post-trabeculectomy, post-laser assisted in situ keratomileusis, post-graft and dacryocystoceles. When combined with warm compresses or other methods of heat delivery to the eye, the elevation of corneal temperature appears to explain how meibomian gland dysfunction treatment involving warm compresses and massage could induce rubbing-related deformation. Patients whose management involves iatrogenic ocular massage appear to require screening for risk of corneal deformation. Risk may be increased for patients with a concurrent habit of rubbing their eyes abnormally in response to allergic itch for example. It appears to be possible to modify ocular massage techniques to reduce the risk of corneal deformation. Careful tutoring and follow-up using corneal topography appears to be required when massage is prescribed, especially when used in conjunction with heat application.

Minimising cornea scarring from the use of harmful traditional eye remedies in developing countries.

Corneal scarring is the fourth largest cause of blindness globally, and a much more prominent factor in developing countries. Blindness from corneal scarring is largely a preventable phenomenon, and is capable of causing significant morbidity that can last for a lifetime. A significant proportion of these cases are caused by the use of harmful traditional eye medicines/remedies, and are used and prescribed by friends, relatives and traditional healers, with widespread use especially in developing countries. Use of traditional remedies can also cause harm indirectly by causing delays before seeking medical treatment. Reducing corneal scarring from the use of harmful traditional medicine is through a combination of approaches with the key strategies being community diagnosis, education, participation, and intervention, with provision of basic eye care integrated into the primary health care of the community. Collaboration with traditional healers in the community is also another approach that has been found to be useful.

Corneal calcific band keratopathy.

PURPOSE OF REVIEW: Calcific band keratopathy is a chronic degenerative condition characterized by the deposition of grayish to whitish opacities in the superficial layers of the cornea. It is usually associated with chronic ocular inflammatory conditions. Various treatment modalities have been used for the management of band keratopathy including mechanical debridement, chelation, and excimer laser phototherapeutic keratectomy (PTK). This review will discuss the cause and management of calcific band keratopathy. RECENT FINDINGS: Recent use of combination treatments such as chelation, excimer laser, and amniotic membrane transplantation has renewed interest in the management of cases with band keratopathy in order to achieve faster epithelial healing and better postoperative outcomes. SUMMARY: Careful case selection is required before deciding on the surgical management plan in cases with band keratopathy. Chelation is a cost-effective and straightforward procedure. An excimer laser PTK, although costly, can provide a smooth corneal surface. Combination treatment using amniotic membrane is reserved for selected cases to enhance epithelial healing.

[Limbal stem cell deficiency following multiple intravitreal injections]. / Insuficiencia limbar secundaria a múltiples inyecciones intravítreas.

CASE REPORT: A 68 year-old male with idiopathic choroidal polypoidal vasculopathy received seven intravitreal injections of bevacizumab in the supero-nasal quadrant. He later developed a localized limbal stem cell deficiency which required limbal transplantation from the same eye. Two months after surgery, a slight improvement of visual acuity was noted, along with an intact ocular surface, clear cornea and decreased inflammation. DISCUSSION: Repeated surgical trauma on the limbus and surrounding areas may damage the limbal stem cells, giving rise to a corneal epitheliopathy due to iatrogenic limbal deficiency. Repeated intravitreal injections may be considered as one of the possible causes.