Diagnosis, Management, and Treatment of Vernal Keratoconjunctivitis in Asia: Recommendations From the Management of Vernal Keratoconjunctivitis in Asia Expert Working Group.

Vernal keratoconjunctivitis (VKC) is an underdiagnosed and underrecognized ocular surface disease with limited epidemiological data in Asia. It is more prevalent in warm, dry, and windy climates, and often has a substantial impact on a patient's quality of life. In rare cases, VKC can be associated with vision loss, either through corticosteroid overuse or inadequate treatment of persistent inflammation. As a potentially severe and complex disease, there is variability with how VKC is managed across Asia and among the various allergic eye diseases. Diagnosis and treatment of patients with VKC is a challenge for many ophthalmologists, since no precise diagnostic criteria have been established, the pathogenesis of the disease is unclear, and anti-allergic treatments are often ineffective in patients with moderate or severe disease. In addition, the choice of treatment and management strategies used for patients varies greatly from country to country and physician to physician. This may be because of a lack of well-defined, standardized guidelines. In response, the Management of Vernal Keratoconjunctivitis in Asia (MOVIA) Expert Working Group (13 experts) completed a consensus program to evaluate, review, and develop best-practice recommendations for the assessment, diagnosis, and management of VKC in Asia. The expert-led recommendations are summarized in this article and based on the currently available evidence alongside the clinical expertise of ophthalmologists from across Asia with specialism and interest in the ocular surface, VKC, and pediatric ophthalmology.

Cataract Surgery Destabilises Temporary the Tear Film of the Ocular Surface. / Kataraktchirurgie destabilisiert vorübergehend die Benetzung der Augenoberfläche.

BACKGROUND: Symptoms due to dry eye in the form of keratoconjunctivitis sicca (KCS) are often seen after cataract surgery. We investigated the influence of cataract surgery on tear film stability on the ocular surface. MATERIAL AND METHODS: 60 eyes of 60 patients who underwent cataract surgery were included in a prospective study in 2017 at the Eye Hospital in Hanoi (Vietnam National Institute of Ophthalmology). The mean age of the patients was 65 ± 10 years. The phacoemulsification was performed under topical anaesthesia by a clear corneal incision and implantation of a foldable IOL. The parameters for the evaluation of the change of the tear film included subjective patient data using the Ocular Surface Disease Index questionnaire (OSDI), findings of the Schirmer I test, the tear break-up time (TBUT) as well as the tear meniscus height (TMH) measured noninvasively with the Keratograph 5M (Oculus). In addition, conjunctival and corneal changes were examined after vital staining with fluorescein for the cornea and rose bengal for the conjunctiva. Data were collected preoperatively, at 1 week, 1 month and 3 months postoperatively. According to DEWS, the disease is classified into 4 groups: mild, moderate, severe and very severe. RESULTS: One week after surgery, the total score according to OSDI was significantly increased with a total value of 14.4 ± 4.2 (p = 0.001). Schirmer I was 15.8 ± 4.3 mm preoperatively and decreased significantly in the first postoperative week (p = 0.001), before reaching the preoperative level again after three months. TBUT was 12.6 ± 1.5 s preoperatively, decreased significantly to 9.7 ± 1.5 s during the first postoperative week, and normalized to 12.4 ± 1.3 s by the end of the third month. The meniscus height was 0.245 ± 0.055 mm preoperatively, significantly lowered to 0.229 ± 0.057 mm in the first postoperative period and nearly normalised by the third postoperative month to 0.241 ± 0.051 mm. In the first postoperative week, the rate of mild KCS was observed in 30% of patients. At one month, this decreased to 10% and at three months was no longer demonstrable in any patient. CONCLUSION: One of three patients experienced mild KCS after cataract surgery. The symptoms lasted up to three months. This should be taken into account preoperatively and appropriate therapy should be planned.

Identification of a Novel Missense KRT12 Mutation in a Vietnamese Family with Meesmann Corneal Dystrophy.

Meesmann epithelial corneal dystrophy (MECD) is a rare dominantly inherited disorder that is characterized by corneal epithelial microcysts and is associated with mutations in the keratin 3 (KRT3) and keratin 12 (KRT12) genes. In this study, we report a novel mutation in the KRT12 gene in a Vietnamese pedigree with MECD. Slit-lamp examination was performed on each of the 7 recruited members of a Vietnamese family to identify characteristic features of MECD. After informed consent was obtained from each individual, genomic DNA was isolated from saliva samples and screening of KRT3and KRT12 genes was performed by Sanger sequencing. The proband, a 31-year-old man, complained of a 1-year history of eye irritation and photophobia. Slit-lamp examination revealed intraepithelial microcysts involving only the corneal periphery in each eye with clear central corneas and no stromal or endothelial involvement. Three family members demonstrated similar intraepithelial microcysts, but with diffuse involvement, extended from limbus to limbus. Sanger sequencing of KRT3 (exon 7) and KRT12 (exons 1 and 6) in the proband revealed a novel heterozygous KRT12 variant (c.1273G>A [p.Glu425Lys]) that was present in the three affected family members but was absent in the three family members with clear corneas. This study is the first report of a Vietnamese family affected with MECD, associated with an atypical peripheral corneal epithelial phenotype in the proband and a novel mutation in KRT12.

Tissue-Cultured Human Cord Lining Epithelial Cells in Treatment of Persistent Corneal Epithelial Defect.

BACKGROUND: Persistent corneal epithelial defect (PED) is a consequence of many ocular surface disorders. Although many therapies have been suggested, the treatment of this disease have faced a lot of difficulties up to now. The transplatation of cultivated amniotic epithelial cells sheets is the new promised method for PED. Cord lining epithelial cells (CLECs) are epithelial cells of amniotic membrane of umbilical cord, so these cultivated cells sheet may be good for treating PED. AIM: To evaluate the efficacy of the transplantation of cultivated CLECs sheets in treatment of PED and analyze some influential factors of this therapy. METHODS: A prospective interventional case series with transplantation of tissue-cultured human CLECs in 37 PED eyes in Vietnam National Institute of Ophthalmology. RESULTS: Thirty four of 37 eyes were healed with the cells transplantation and 22 eyes of them healed within a week postoperatively. There were normal corneal scars and normal corneal epithelial cell (by impression cytology detection) on transplantation site in all 31 successful cases. The other successful eyes were done lamellar keratoplasty (respectively in 1 month, 3 months, 6 months and 27 months postoperatively) to investigate the histopathology of the CLECs transplant site. The histopathological images showed normal corneal scar and there was no appearance of CLECs in transplant site. CONCLUSION: tissue-cultured human CLECs transplantation is a quite safe and effective treatment for persistent corneal epithelial defect. The CLECs may help the epithelial healing at early stage but do not exist at transplant site for a long time.

Penetrating Keratoplasty for Keratoconus in Vietnamese Patients.

BACKGROUND: Keratoconus is an ectatic corneal disorder that can impair the visual acuity. Up to now, penetrating keratoplasty (PK) remains the most common surgical procedure to treat severe keratoconus. In Vietnam, most keratoconus patients come to visit doctor at severe stage and were treated by PK, so we conduct this study. AIM: To evaluate the results of PK for keratoconus in Vietnamese patients. METHODS: This was a retrospective study of 31 eyes with keratoconus who underwent PK in VNIO from January 2005 to December 2014. RESULTS: The average visual acuity was 0.86 ± 0.37 logMAR (20/145). In the group of patients without amblyopia, best spectacle-corrected visual acuity of 20/60 or better was recorded in 75.9% of eyes and 93.1% of eyes achieved a best corrected visual acuity with hard contact lenses of 20/40 or better. Mean postoperative corneal power was 43.8 ± 4.5D. Mean corneal astigmatism was 5.9 ± 2.7D. 94.6% of grafts remained clear. Posterior subcapsular cataract developed in 22.6% of eyes. Graft rejection was recognized in 12.9% of eyes. CONCLUSION: PK is an effective procedure with high rate of graft survival for keratoconus patients. However, patients should be aware of the necessary of optical correction to gain the best VA after surgery.

Evaluation of Phacoemulsification Cataract Surgery Outcomes After Penetrating Keratoplasty.

BACKGROUND: Cataract is one of the reasons which causes impaired visual acuity (VA) of the eyes after penetrating keratoplasy (PK), which can be treated by cataract surgery after PK or triple procedure. Cataract surgery after PK has advantages that parameters of the eyes such as axial length, anterior chamber depth (ACD) as well as corneal curvature are stabilized after removing all sutures postoperatively, and intraocular lens (IOL) power can be calculated correctly. Therefore, postoperative VA will be improved significantly. In Vietnam, there have not been any study about cataract surgery after PK, therefore we conduct this research. AIM: To evaluate the outcomes of phacoemulsification cataract surgery following primary PK. METHODS: Non-randomized controlled intervention study. Ninteen eyes (19 patients) that underwent phacoemulsification plus IOL insertion after initial PK in Cornea department, Vietnam National Institute of Ophthalmology, from December 2013 to September 2014. RESULTS: All patients presented with reduced VA, including 17 eyes (89.9%) with VA ≤ 20/200, mean astigmatism was 7.9 ± 1.0 D. Clear corneal grafts in 16 eyes while corneal opacity was seen in 3 eyes. All eyes with cataract were diagnosed from grade 2. After cataract surgery, improved VA > 20/200 was achieved in 72.22% of cases. There was a markable reduce of postoperative astigmatism with 1.8 ± 0.8 D (p < 0.05). However, the immunologic graft reaction was presented in one eye, and two edematous corneas also reported after cataract surgery. After treatment, there was one cornea achieved its clarity. CONCLUSION: Phacoemulsification cataract surgery following initial PK showed good outcomes with improved postoperative VA, reduced astigmatism, and the ultimate graft survival rate was high.

Bullous Keratopathy Secondary to Anterior Chamber Angle Foreign Body.

BACKGROUND: Penetrating ocular trauma with intraocular foreign body is a serious injury often resulting in loss of vision. Anterior chamber foreign bodies account for a considerable portion of all cases of all intraocular foreign bodies (up to 15%); however, they can be missed due to inconspicuous location. CASE REPORT: We report two cases of retained intraocular foreign bodies in the iridocorneal angle that was missed at the first ophthalmic examination. They were only discovered when complications occurred, such as corneal edema and increased intraocular pressure. In the case whereby the foreign body was taken out early, corneal damages were reversible. However, in the case whereby the foreign body was taken out late, endothelial damage was irreversible and endothelial transplantation was needed. CONCLUSION: Regarding trauma patients, a careful examination should be performed to discover foreign bodies in the iridocorneal angle. If local peripheral corneal edema occurred, attention should be paid to the trauma history and to timely discovery of the foreign body. This will prevent any irreversible corneal damages.

Mutation analysis of the TGFBI gene in Vietnamese with granular and Avellino corneal dystrophy.

PURPOSE: Mutations of the human transforming growth factor beta-induced gene (TGFBI) were reported to cause granular (GCD) and Avellino (ACD) corneal dystrophy in various nationalities. In this study we examined the TGFBI gene in a Vietnamese population with GCD and ACD. METHODS: Eight unrelated Vietnamese families, including 20 affected and 24 unaffected individuals, were examined; 50 normal Vietnamese individuals were used as controls. Genomic DNA was extracted from peripheral blood leukocytes. The TGFBI gene was analyzed using the polymerase chain reaction and direct sequencing. The corneal button was studied. RESULTS: Slit-lamp examination revealed typical features of GCD in most cases. A few features of ACD and a patient with an atypical form of GCD were also seen. Histopathological analysis of a GCD cornea showed deposits that stained bright red with Masson trichrome. Sequencing revealed three distinct mutations: R555W in six families, R124H in one family, and D123H in another. CONCLUSIONS: R555W and R124H mutations were co-segregated with the disease phenotype and thus caused GCD and ACD, respectively, in the families studied. The R555W detected in six of the eight families indicates that the GCD phenotype may be the most common in Vietnamese individuals, unlike in other Asians (Japanese and Korean), where ACD is most common (>90%). The D123H mutation may cause an atypical variant of GCD.

Mutation analysis of the carbohydrate sulfotransferase gene in Vietnamese with macular corneal dystrophy.

PURPOSE: Mutations in a new carbohydrate sulfotransferase gene (CHST6) encoding corneal N-acetylglucosamine-6-sulfotransferase (C-GlcNac-6-ST) have been identified as the cause of macular corneal dystrophy (MCD) in various ethnicities. This study was conducted to examine the CHST6 gene in Vietnamese with MCD. METHODS: Nineteen unrelated families, including 35 patients and 38 unaffected relatives were examined clinically. Blood samples were collected. Fifty normal Vietnamese individuals served as control subjects. Genomic DNA was extracted from leukocytes. Analysis of the CHST6 gene was performed with polymerase chain reaction and direct sequencing. Corneal buttons were studied histopathologically. RESULTS: A slit lamp examination revealed clinical features of MCD with gray-white opacities and stromal haze between. On histopathology, corneal sections showed positive staining with colloidal iron. Sequencing of the CHST6 gene revealed six homozygous and three compound heterozygous mutations. The homozygous mutations, including L59P, V66L, R211Q, W232X, Y268C, and 1067-1068ins(GGCCGTG) were detected, respectively, in two, one, eight, one, one, and two families. Compound heterozygous mutations R211Q/Q82X, S51L/Y268C, and Y268C/1067-1068ins(GGCCGTG) were identified, each in one family. A single heterozygous change at codon 76 (GTG-->ATG) was detected in family L, resulting in a valine-to-methionine substitution (V76M). None of these mutations was detected in the control group. CONCLUSIONS: Mutations identified in the CHST6 gene cosegregated with the disease phenotype in all but one family studied and thus caused MCD. Among these, the R211Q detected in 9 of 19 families may be the most common mutation in Vietnamese. These data also indicate that significant allelic heterogeneity exists for MCD.

Identification of novel mutations of the CHST6 gene in Vietnamese families affected with macular corneal dystrophy in two generations.

PURPOSE: To report the clinical and genetic findings of Vietnamese families affected with macular corneal dystrophy (MCD) in 2 generations. METHODS: Two families, including 7 patients and 3 unaffected members, were examined clinically. Blood samples were collected. Fifty normal Vietnamese individuals were used as controls. Genomic DNA was extracted from leukocytes. Analysis of the carbohydrate sulfotransferase (CHST6) gene was performed using polymerase chain reaction and direct sequencing. RESULTS: The typical form of MCD was recognized in family B, in which sequencing of CHST6 gene revealed an nt 1067-1068ins(GGCCGTG) mutation (frameshift after 125V) homozygously in MCD patients and heterozygously in the unaffected members. Family N also showed clinical features of MCD, moderate in the mother but severe in the affected son. Sequencing revealed a single heterozygous Arg211Gln in the mother, compound heterozygous Arg211Gln+ Gln82Stop in the affected son, and heterozygous Arg211Gln mutation in the unaffected members. The identified mutations in these pedigrees were excluded from normal controls. CONCLUSIONS: The novel frameshift and compound heterozygous mutations might be responsible for MCD in the families studied. The phenotypic variation between affected parents and offspring was unclear. In family N, severe MCD phenotype seen in the affected son may be due the fact that he had an early stop codon mutation (Gln82Stop).

A novel mutation of the TGFBI gene found in a Vietnamese family with atypical granular corneal dystrophy.

BACKGROUND: Mutation of the human transforming growth factor beta-induced (TGFBI) gene causes granular corneal dystrophy (GCD) in various ethnic groups. In this report, we identify the genetic defect on the TGFBI gene in a Vietnamese family with atypical GCD . CASES: The patient and her relatives were examined clinically. Genomic DNA was extracted from blood leukocytes. Fifty normal Vietnamese were used as controls. Analysis of the TGFBI gene was performed using polymerase chain reaction and direct sequencing. OBSERVATIONS: The 42-year-old proband clinically showed multiple white dot-like opacities scattered in the anterior and mid-stroma of the central cornea. Unlike GCD, these deposits were smaller, localized deeper and less severe. DNA analysis revealed a nucleotide transversion at codon 123 (GAC --> CAC), causing Asp --> His substitution (D123H). This mutation was also detected in 3 out of 5 unaffected family members, but was absent in the 50 normal controls. CONCLUSIONS: The novel D123H mutation of the TGFBI gene was not co-segregated with GCD in the family studied, and did not exist in the control population. It probably was a disease-causing mutation, thus expected to cause a novel variant of GCD in the proband. The detection of the D123H mutation in three unaffected family members indicates that it has low penetrance for GCD.

A novel mutation of M1S1 gene found in a Vietnamese patient with gelatinous droplike corneal dystrophy.

To identify the genetic defect in the M1S1 gene responsible for gelatinous droplike corneal dystrophy (GDLD) in a Vietnamese family.Experimental study. Blood samples were collected from a patient and the unaffected members of a GDLD-affected family. Fifty normal unrelated subjects of Vietnamese origin were used as controls. Genomic DNA was extracted from blood leukocytes. DNA analysis of the M1S1 gene was performed using polymerase chain reaction and direct sequencing. Sequencing of the M1S1 gene revealed a deletion of a 12-base-pair (bp) fragment from nucleotide positions 772 to 783 [772 to 783del(ATCTATTACCTG)], resulting in a loss of four amino acids at codons 258 to 261 (L258-liter261del). Yet, an insertion of nucleotide T in place of the missing sequence (772insT) was found. This combined mutation was homozygous in the GDLD-affected patient and heterozygous in his unaffected son and younger sister. Such genetic alteration was excluded in the control population. This is the first report of a mutational analysis performed in a Vietnamese patient with GDLD. In this family, the novel 772 to 783del(ATCTATTACCTG) + 772insT mutation on the M1S1 gene was well cosegregated with the phenotype and thus expected to cause GDLD. Although the M1S1 gene was responsible for GDLD in Vietnamese patients, the mutation found here is completely different from that previously reported in Japanese patients, where GDLD is most frequently seen.