Effects on Intravitreal Anti-vascular Endothelial Growth Factor Injections during the COVID-19 Pandemic in the Eastern Black Sea Region of Turkey.

Objectives: To compare the number of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections performed during 2020 with that in the same period in 2019. Methods: The study investigated anti-VEGF injections performed in 2019 and 2020. Injections performed on 923 eyes of 858 patients were evaluated. The patients were treated for diabetic macular edema (DME), age-related macular degeneration (AMD), and retinal vein occlusion (RVO). Injections, new cases, and patients who either completed or did not complete three loading doses in 2019 and 2020 were first compared. The same comparisons were then performed between the pandemic period in 2020 and the same period in 2019. Results: While 2070 injections were performed on 670 eyes in 2019, 1478 injections were applied to 253 eyes in 2020 (p=0.001). The number of naive eyes was 163 in 2019 and 83 in 2020. During the pandemic period in 2020, 967 injections were performed on 181 eyes, compared with 1721 injections on 532 eyes in the same period in 2019 (p=0.001). While 86.5% of patients completed three injections in 2020, the rate was 78.9% for the same period in 2019 (p=0.025). Conclusion: The COVID-19 pandemic caused a significant decrease in the number of patients presenting to the hospital, and delays occurred in treatment protocols. However, patients admitted to the hospital during this period adapted better to the loading doses. In conclusion, the pandemic caused significant disruption to treatment, and this will inevitably result in anatomical and functional worsening in the eye.

The clinical use of ultra - Wide field imaging and intravenous fluorescein angiography in infants with retinopathy of prematurity.

PURPOSE: To investigate the potential benefits and practicality of ultra - wide field (UWF) imaging and intravenous UWF fluorescein angiography (IV UWF - FA) in infants with retinopathy of prematurity (ROP) using an Optos® California device. METHODS: This retrospective study involved 46 infants with a history of ROP who underwent UWF imaging with or without IV UWF - FA. ROP characteristics were identified using UWF color imaging. Retinal vascular findings following treatment were also assessed at IV UWF - FA analysis. All imaging sessions were performed under topical anesthesia without sedation. Main outcomes were the appearance of ROP at UWF color imaging and IV UWF-FA analysis, including status of ROP, neovascularizations, presence of plus disease, retinal vascular details, and resolution after treatment. RESULTS: Seven (three girls) of the 46 infants (22 girls) underwent IV UWF-FA. Twelve IV UWF-FA sessions were performed in total. The oldest infant during IV UWF-FA analysis was at 55 postmenstrual weeks. Clinical characteristics of disease were easily identified at UWF color imaging. IV UWF-FA images also clearly revealed non-perfused retinal areas, fluorescein leakage, macular edema, retinal vascular abnormalities, and the status of the peripheral vascular termini. Complications of IV UWF-FA occurred in one infant in the form of patchy yellow skin discoloration around the injection site which completely disappeared on the first day following the procedure. CONCLUSIONS: Providing a high resolution panoramic view of the retina in a single image capture with no need for contact with the cornea appear to represent potential advantages of UWF imaging in infants with ROP. IV UWF-FA also seems to be a safe procedure which can be performed under topical anesthesia and that shows detailed retinal vascular alterations in patients with ROP.

Infliximab therapy provides beneficial effects for choroidal thickness increase in patients with active ankylosing spondylitis: A possible mechanism mediating the suppressing of uveitis attacks.

OBJECTIVES: This study aims to quantitatively assess the profile of the choroidal thickness (ChT) in patients with ankylosing spondylitis (AS) using optical coherence tomography (OCT), and to examine whether the posterior eye segment abnormalities in active AS patients are reversible by infliximab therapy. PATIENTS AND METHODS: October 2014 and March 2016 Thirty-one patients with AS (22 males, 9 females; mean age 39.6±12.3 years; range, 22 to 68 years) and 24 healthy controls (16 males, 8 females; mean age 40.8±8.9 years; range, 35 to 61 years) were enrolled. Patients' clinical and demographic characteristics were recorded. Using OCT, we performed retinal nerve fiber layer (RNFL) thickness, ganglion cell complex, and ChT measurements in AS patients before and six months after the initiation of infliximab therapy, and in healthy controls. RESULTS: At baseline, patients with AS had higher ChT (mean±standard deviation: 347.5±114.4 µm) compared to healthy controls (322.1±62.8 µm), although this did not reach statistical significance level (p=0.283). At six months after the first measurement, the mean ChT was significantly decreased (under infliximab therapy: 326.5±99.7 µm vs. before: 347.5±114.4 µm, p=0.018) in AS group, while no significant change was observed in the control group (p=0.102). RNFL thickness in the AS group was significantly decreased after six months of treatment with infliximab (p=0.008). CONCLUSION: By evaluating the posterior eye segment of patients with AS using OCT, this study has demonstrated that active AS patients had higher ChT. The significant reduction in this ChT after infliximab therapy may be mediating the established effective suppressing action of infliximab on uveitis attacks.

The role of simple inflammatory blood parameters in idiopathic epiretinal membrane patients.

AIM: To evaluate the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in idiopathic epiretinal membrane (IERM) patients, and their relations with visual acuity. METHOD: Fifty-seven IERM and 51 control patients were included. All patients underwent comprehensive ophthalmological examination and complete blood count tests, and NLR and PLR values were calculated. Patients with IERM were compared with the control group, and associations with visual prognosis were evaluated. These ratios' cut-off values for IERM were also calculated RESULTS: NLR values were statistically significantly higher in the IERM group than in the control group (p = 0.001). No significant difference was observed between the IERM and control groups in terms of PLR (p = 0.43). No significant correlation was determined between visual acuity and NLR or PLR (r = 0.05, p = 0.66; and r = 0.18, p = 0.16, respectively). The cut-off value for NLR was 1.91. CONCLUSION: Patients with IERM showed significantly increased NLR compared to control subjects suggesting that IERM patients may be prone to have high NLR values.

The efficacy of subthreshold micropulse yellow laser (577 nm) in chronic central serous chorioretinopathy.

Central serous chorioretinopathy (CSC) is a disease characterized by a well-defined serous detachment of the neurosensory retina. Therapeutic options in chronic cases are limited, and side effects can result in a limited response. The aim of this article is to assess the efficacy of subthreshold micropulse laser therapy in patients with chronic central serous chorioretinopathy. The study included 20 eyes of 19 patients who had a history of chronic or chronic recurrent CSC and who underwent subthreshold micropulse laser therapy between January 2015 and June 2018. Twenty eyes of 19 patients with a mean age of 48.9 ± 9.40 years were included. The mean visual acuity was 0.24 ± 0.28 logMAR before laser, 0.19 ± 0.25 logMAR 3 months after laser, and 0.18 ± 0.27 logMAR after 6 months. A statistically significant difference was determined in terms of visual acuity before and after treatment (p = 0.0001). The mean central retinal thickness was 308.10 ± 95.25 µm before laser, 233.65 ± 81.17 µm 3 months after laser, and 203.88 ± 72.79 µm at 6 months. A statistically significant relationship was present between visual acuity and the duration of disease (p = 0.001), between visual acuity and the outer nuclear layer thickness (p = 0.005), and between the outer nuclear layer thickness and the duration of disease in chronic cases (p = 0.008). There was no evidence of retinal pigment epithelium or retinal damage on optical coherence tomography or fundus autofluorescence secondary to subthreshold micropulse laser therapy. Visual acuity appears to be more associated with the duration of disease and with changes in the outer nuclear layer thickness in chronic CSC. Subthreshold micropulse laser therapy seems to be effective at treating chronic CSC, while it increases success during early period of the disease before the development of permanent retinal damage.

Sedoanalgesia modality during laser photocoagulation for retinopathy of prematurity: Intraoperative complications and early postoperative follow-up.

BACKGROUND: Laser photocoagulation (LPC) is a surgical procedure used in the treatment of premature retinopathy that may cause retinal detachment and blindness if not diagnosed and treated early. The anesthesia method used in LPC varies from sedoanalgesia to general anesthesia and airway management varies from spontaneous ventilation to endotracheal intubation. In this study, we aimed to evaluate the effectiveness of sedoanalgesia applications and this anesthesia procedure concerning intraoperative and postoperative complications by avoiding intubation and mechanical ventilation in premature infants with a fragile population. METHODS: This retrospective study included 89 patients who underwent laser photocoagulation under anesthesia for premature retinopathy. Patients' demographic characteristics, preoperative risk factors, anesthesia technique, especially airway management, changes in ventilation status during surgery, intraoperative complications, postoperative complications, and intensive care follow-up, were recorded and analyzed statistically. RESULTS: Two of the 89 patients who underwent laser photocoagulation were excluded from this study because they were followed up intubated. The number of patients who received mask ventilation due to intraoperative complications was 12 (13.8%). The mean operation time was 36.2±10.1 minutes. In 86.2% (n=75) of the patients, the surgical procedure was completed with sedoanalgesia while maintaining spontaneous ventilation. CONCLUSION: Sedoanalgesia application during the surgical intervention of patients with Retinopathy of Prematurity (ROP) requiring early diagnosis and emergency treatment will minimize intraoperative and postoperative complications. We believe that sedoanalgesia as an anesthetic method can be applied as an effective alternative method while preserving spontaneous ventilation.

Wernicke`s encephalopathy manifesting with diplopia after ileojejunostomy: report of a pediatric case with Hirschsprung disease.

BACKGROUND: Wernicke`s encephalopathy (WE) is a coenzyme-induced disease with acute neuropsychiatric symptoms leading to high mortality and morbidity due to thiamine deficiency. WE is mostly caused by alcoholism in adult populations; however, it is often associated with gastrointestinal surgical procedures, recurrent vomiting, chronic diarrhea, cancer and chemotherapy treatment, systemic diseases, drugs, magnesium deficiency, and malnutrition in children. Although these predisposing factors are considered to be uncommon in children, they are actually highly frequent and can be fatal if not treated promptly. CASE: In this report, we present a patient who developed diplopia during total parenteral nutrition following surgical resection and was diagnosed with WE. The findings of the patient's cranial magnetic resonance imaging (MRI) findings were consistent with those of WE and the ocular findings of the patient resolved completely after thiamine treatment. CONCLUSION: Although WE is rare in children it can be prevented by early diagnosis and treatment and oculomotor findings such as diplopia can be a warning sign.

Characteristics and Seasonal Variations of Rhegmatogenous Retinal Detachment in the Eastern Black Sea Region of Turkey: 8-Year Results.

Objectives: To assess seasonal variations in the incidence of rhegmatogenous retinal detachment (RRD) in the Eastern Black Sea region of Turkey. Materials and Methods: Patients presenting due to primary RRD to a university hospital operating as a reference clinic in the region between 2011 and 2018 were evaluated retrospectively. Patients' ages, sex, affected eye, and presentation times were recorded. Years were divided into months, quarters, seasons, and half-year periods, and these periods were analyzed in terms of differences in patient numbers. Results: Two hundred eighty-one eyes of 276 patients meeting the study criteria were included. The patients' mean age was 60.2 years, and the male:female ratio was 1.35:1. Right and left eye rates were similar. Detachments were most common (49.4%) in the upper temporal quadrant. Eighty-nine patients (31.6%) had undergone uncomplicated phacoemulsification surgery a mean 2.7 years previously. The mean annual case number was 35.13±5.43, and no statistically significant variation was determined in case numbers by year (p=0.558). Analysis of all years revealed a monthly mean case number of 23.42±4.4, with the highest number of cases, 29 (10.3%), being seen in September and the lowest number, 13 (4.7%), in December. No statistically significant monthly variation was determined (p=0.613). Similarly, no statistically significant variation was observed in case numbers analyzed by quarter, season, or half-year (p>0.05). Conclusion: The incidence of cases of uncomplicated RRD does not exhibit seasonal variation in our region. We also think that since 31.6% had a history of cataract surgery, patients undergoing phacoemulsification surgery, even if uncomplicated, should be periodically assessed for detachment.

Repeatability and Agreement of Macular Thickness Measurements Obtained with Two Different Scan Modes of the Optovue RTVue Optical Coherence Tomography Device

Objectives: To evaluate the repeatability and agreement of macular thickness measurements obtained with E-MM5 and MM6, two different scan modes, on the Optovue RTVue optic coherence tomography (OCT) device. Materials and Methods: Three consecutive macular thickness measurements in 30 healthy volunteers were taken using the OCT device E-MM5 and MM6 scan modes. The repeatability and agreement of these measurements obtained from the two scan modes and divided into nine anatomical regions based on early treatment diabetic retinopathy study were subjected to statistical analysis. Results: The mean age of the participants was 29.7±6.39 years. Intraclass correlation (all ICC values ≥0.86) and coefficient of variation (all coefficient of variation values ≤2%) analyses of consecutive OCT measurements in the nine regions of the macula obtained in both E-MM5 and MM6 scan modes gave high repeatability rates. Mean macular thickness values in the foveal region were 243.76±21.79 µm in E-MM5 mode and 247.04±19.83 µm in MM6 mode (p=0.543). Values for measurements obtained in E-MM5 and MM6 scan modes in parafoveal macular regions were also statistically similar (p>0.05 for all). However, a statistically significant difference was observed between the two modes in perifoveal macular measurements, except in the superior region. Conclusion: The Optovue RTVue OCT device gives highly repeatable measurement results for macular thicknesses in both E-MM5 and MM6 scan modes. However, it should be considered that measurements performed in E-MM5 and MM6 modes give different results in perifoveal regions.

Bilateral acute angle closure developing due to use of ipratropium bromide and salbutamol.

Acute angle closure can be seen as a side effect of some medications that can be used systemically. In this article, clinical characteristics of 54-year-old female patient who applied to our clinic with bilateral acute angle closure and has been received nebulized form of salbutamol and ipratropium bromide due to asthma for 4 days was evaluated. Right and left eye IOP were measured as 50 and 48 mmHg. IOP was reduced with anti-glaucomatous treatment. and peripheral iridectomy was done, and then the patient was discharged. It is necessary to be careful to prevent contact with the eye of nebulized form of these drugs which may result in angle closure glaucoma when used systemically.

ACCIDENTAL DUPLICATION: Investigation of the effect of hemoglobin F and A levels on development of retinopathy of prematurity.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.jaapos.2017.03.006. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Evaluation of the effects on choroidal thickness of bimatoprost 0.03% versus a brinzolamide 1.0%/timolol maleate 0.5% fixed combination.

OBJECTIVE: To investigate the effects of two different medical treatment options on choroidal thickness (CT) in cases of open-angle glaucoma (OAG). METHODS: Sixty-seven eyes newly diagnosed with OAG and 52 healthy eyes constituting the control group were included in the study. Glaucomatous eyes were randomly divided into two subgroups; Group I was started on bimatoprost 0.03% and Group II on a brinzolamide 1.0%/timolol maleate 0.5% fixed combination (BTFC). Intraocular pressure (IOP), ocular pulse amplitude (OPA) and subfoveal CT measurements were performed in all eyes in the study before treatment and on weeks 2, 4 and 8 after treatment. RESULTS: Mean initial IOP values in groups I and II and the control group were 25.5 ± 4.7, 25.1 ± 5.2 and 16.1 ± 2.9 mmHg, mean OPA values were 3.7 ± 1, 3.6 ± 1.4 and 2.4 ± 0.6 mmHg and mean CT values were 269.4 ± 83, 264.5 ± 84.4 and 320.1 ± 56.6 µm, respectively. Eight weeks after treatment, mean IOP values in Groups I and II and the control group were 18.3 ± 2.6, 18.1 ± 3.4 and 15.7 ± 2.9 mmHg, mean OPA values were 2.9 ± 1.2, 2.8 ± 1.5 and 2.3 ± 0.8 mmHg and mean CT values were 290.2 ± 87.3, 271.8 ± 82.5 and 319.3 ± 56.8 µm, respectively. No significant difference was determined in terms of the decrease in IOP and OPA obtained after treatment in Group I and Group II. However, a significant difference was observed between the two groups in terms of choroidal thickening after treatment. CONCLUSION: The use of topical ocular hypotensive medication in eyes with OAG results in an increase in CT. This increase is relatively greater with bimatoprost 0.03% therapy compared to BTFC.

Investigation of the effect of hemoglobin F and A levels on development of retinopathy of prematurity.

PURPOSE: To investigate the effect of hemoglobin F (HbF) and hemoglobin A (HbA) levels on development of retinopathy of prematurity (ROP) in premature infants. METHODS: In this prospective study, blood samples were collected from the side of the heel of 49 premature infants at postnatal months 0, 1, 2, and 3. HbF and HbA levels were measured in all samples and analyzed statistically. Furthermore, correlation analysis was performed regarding development of ROP, blood transfusion, and HbF and HbA levels. RESULTS: A total of 49 infants were included. The mean gestational age of the premature infants was 30.9 ± 2.7 weeks (range, 25-35 weeks); mean birth weight, 1542 ± 582 g (range, 520-3240 g). Of the 49 premature infants, stage 1 ROP or above developed in 26 (53%). Mean HbF levels were lower at postnatal months 1 and 2 in premature infants with ROP compared to those without ROP (P = 0.013 and 0.02, respectively); however, mean HbA levels were higher in the infants with ROP than the others (P = 0.034 and 0.029, respectively). Analysis of covariance that ignored transfusion revealed no difference between the means of Hb variants in the infants with and without ROP (P = 0.572 and 0.486). CONCLUSIONS: Blood transfusion significantly altered the levels of HbF and HbA in premature infants, and Hb variants have no direct effect on development of ROP.

Evaluation of Retinal Changes Using Optical Coherence Tomography in a Pediatric Case of Susac Syndrome.

Susac syndrome is a rare occlusive vasculopathy affecting the retina, inner ear and brain. The cause is unknown, although it generally affects young women. This syndrome can be difficult to diagnose because its signs can only be revealed by detailed examination. These signs are not always concomitant, but may appear at different times. This report describes a pediatric case who was diagnosed with Susac syndrome when retinal lesions were identified in the inactive period with the help of optical coherence tomography (OCT). The purpose of this case report is to emphasize the importance of OCT in clarifying undefined retinal changes in Susac syndrome.

Determination of regional screening criteria for retinopathy ofprematurity in the Eastern Black Sea region of Turkey.

BACKGROUND/AIM: To establish a regional screening protocol for retinopathy of prematurity (ROP). MATERIALS AND METHODS: Data were analyzed from the hospital records of 1241 infants with gestational age (GA) at birth ≤36 weeks and birth weight (BW) of ≤3600 g. RESULTS: The mean GA of the infants was 32.05 ± 2.7 weeks and the mean BW was 1780.5 ± 576 g. ROP at any stage was detected in 703 of the 1241 infants (555 female). Eleven infants with type 1 ROP were treated with 810 nm diode laser photocoagulation. No treatment was needed in infants born after 33 weeks of gestation and weighing over 1760 g. Logistic regression analysis showed a significant relationship between the development of ROP and GA, BW, number of deliveries, respiratory distress syndrome, and treatment with oxygen or mechanical ventilation. Receiver operating characteristic curve analysis showed that a GA of 33 weeks or a BW of 1770 g appears to be an appropriate criterion for identifying infants who may require ROP treatment. CONCLUSION: GA ≤ 33 weeks and BW ≤ 1770 g can be used as screening criteria in terms of ROP in infants for the Eastern Black Sea region.

The effectiveness and reliability of posterior sub-Tenon triamcinolone acetonide injection in branch retinal vein occlusion-related macular edema.

OBJECTIVE: To investigate the effectiveness and reliability of posterior sub-Tenon triamcinolone acetonide (PSTA) application in branch retinal vein occlusion (BRVO)-related macular edema. METHODS: Patients with confirmed BRVO-related macular edema were enrolled in the study. Patients were injected with a single, therapeutic dose of 40 mg PSTA. Detailed ophthalmic examination was performed at baseline and at 1, 3 and 6 months after the treatment. Best corrected visual acuity (BCVA), intraocular pressure (IOP), cataractogenic change (CC) and macular optical coherence tomography (OCT) analysis results were evaluated. The results were compared statistically. RESULTS: Forty-one eyes of 41 patients with a mean age of 63.49 ± 10.99 (55-86) years, 15 (36.6%) females, were included in the study. BCVA in LogMAR values at 1 and 3 months were significantly better than at baseline, while no significant difference from baseline was observed in sixth month values (p < 0.001, p < 0.001 and p = 0.846, respectively). Central macular thickness values obtained using OCT were significantly lower at the first, third and sixth months compared to baseline (p < 0.001 for all). IOP elevation was determined in only two eyes (4.8%) at the end of the study period, and no CC was detected in any case. CONCLUSION: PSTA application is an effective and safe option in BRVO-related macular edema.

Comparison of brimonidine-timolol and dorzolamide-timolol in the management of intraocular pressure increase after phacoemulsification.

AIM: To compare the effectiveness of brimonidine/timolol fixed combination (BTFC) and dorzolamide/timolol fixed combination (DTFC) in the management of short-term intraocular pressure (IOP) increase after phacoemulsification surgery. METHODS: Eighty eyes of 80 patients undergoing phacoemulsification and intraocular lens (IOL) implantation were randomly assigned into three groups. Group 1 consisted of 28 eyes and represented the control group. Group 2 consisted of 25 eyes undergoing phacoemulsification surgery and BTFC was instilled at the end of surgery. Group 3 consisted of 27 eyes undergoing phacoemulsification surgery and DTFC was instilled at the end of surgery. IOP was measured preoperatively and 6, 24h and 1wk postoperatively. RESULTS: There was no statistically significant difference in preoperative baseline IOP among the three groups (P=0.84). However, IOP was significantly lower in groups 2 and 3 compared to the control group (P<0.05 for all comparisons) at all postoperative visits. There was no significant difference between groups 2 and 3 at any visit. Eight eyes (28.6%) in the control group, two (8%) in Group 2 and one (3.7%) in Group 3 had IOP >25 mm Hg at 6h after surgery (P=0.008). However, IOP decreased and was >25 mm Hg in only one eye in each group at 24h after surgery. CONCLUSION: BTFC and DTFC have similar effects in reducing increases in IOP after phacoemulsification surgery and can both be recommended for preventing IOP spikes after such surgery.

[Primary Neisseria meningitidis conjunctivitis in a 14-month-old child]. / On dört aylik bir çocukta primer Neisseria meningitidis konjonktiviti.

Meningococcal conjunctivitis is a rare but important infection since it can lead to severe complications and can threaten public health. It may emerge in two forms, either primary or secondary type which is developed after a systemic infection. Accurate diagnosis of primary meningococcal conjunctivitis is very important in addition to ocular complications which can result in loss of vision, the condition can also lead to severe complications like systemic meningococcal disease. However, the lack of specific symptoms which can distinguish meningococcal conjunctivitis from other forms of bacterial conjunctivitis, initiation of empiric antibiotic therapy without performing culture and nonaccurate differentiation of Neisseria gonorrhoeae and Neisseria meningitidis with commercial kits/systems used in laboratories cause problematic situations. This report describes a case of primary unilateral conjunctivitis in a 14-month-old girl caused by non-groupable N.meningitidis that was resolved without sequelae following treatment. A pre-healthy 14-month-old girl was brought to the pediatric emergency department with redness, crusts and discharge in the left eye that had begun two days earlier. Ocular examination revealed hyperemia and purulent discharge in the left conjunctiva. Purulent conjunctivitis was diagnosed. A conjunctival swab specimen was taken for culture, and the patient was started on topical netilmicin (4x1), topical fusidic acid (2x1) and artificial tears. Microscopic examination of the conjunctival swab revealed polymorphonuclear leukocytes and no visible bacteria. Catalase and oxidase positive, gram-negative diplococci grew purely in culture. The first Gram stain preparation was evaluated again after the growth and small numbers of gram-negative diplococci were observed. The cultivated bacteria were identified as N.meningitidis using MALDI-TOF MS (Bruker Daltonics, Germany), but as N.gonorrhoeae with BBL Crystal N/H (Neisseria/Haemophilus) (BD Diagnostic Systems, MD) identification system. The isolate was identified as N.meningitidis by polymerase chain reaction method. The isolate was sent to the Public Health Institution of Turkey for confirmation and serotyping. It was confirmed as non-groupable N.meningitidis. This is the first report of conjunctivitis caused by non-groupable N.meningitidis from Turkey. We wish to emphasize the importance of Gram staining and differentiation of the species by automatized systems in diagnosis, netilmicin may be one of the options for empiric treatment and in terms of public health the most appropriate approach may be evaluation of the severity of conjunctivitis and causative serogroup which depends on case-based approach.